ToxTalk EditorsYale Caplan, Ph.D., DABFTVickie Watts, M.S.

Section EditorsDaniel Anderson, M.S.Matthew Barnhill, Ph.D., DABFTDwain Fuller, B.S.Donald Kippenberger, Ph.D.

SOFT 2007 Board of DirectorsPRESIDENT

Diana Wilkins, Ph.D.VICE PRESIDENT

Christine Moore, Ph.D., DABCCSECRETARY

Anthony Costantino, Ph.D., DABFTTREASURER

Bradford Hepler, Ph.D., DABFTWEBMASTER

Bruce Goldberger, Ph.D., DABFTDIRECTORS

Philip Kemp, Ph.D., DABFTBarry Logan, Ph.D., DABFTAshraf Mozayani, Ph.D., DABFTMarc LeBeau, Ph.D.Sarah Kerrigan, Ph.D.

ex officio:Past President:

Timothy Rohrig, Ph.D., DABFTWebmaster:

Bruce Goldberger, Ph.D., DABFTToxTalk Editors:

Yale Caplan, Ph.D., DABFTVickie Watts, M.S.

I N S I D E T H I S I S S U E :President’s Message 22007 Meeting Review 3-52007 Pictures from Meeting 6-9Treasurer’s Report 10-11Drugs In The News 12-15Case Notes 16-17Survey Feedback Report 18ABFT /Member News 19

Inserts:2008 Dues Form2008 Mtg. Prelim. Program / Welcome2008 Workshop Proposal - 2008 Mtg.2008 Call for Papers JAT Special Issue

WOW! S.O.F.T. 2007 came and wentin a flurry to Raleigh-Durham, North Carolina.The Planning Committee worked long and hardto bring the membership a memorable meetingand at the end of the week we felt confident itshowed!

This meeting carried on the S.O.F.T.traditions of superior scientific presentationsand educational opportunities, high-energysocial engagements, and non-stop professionaldevelopment. As part of the business meetingreport, the Planning Committee shared meetingstatistics and would like to share these finalstatistics in ToxTalk. S.O.F.T. 2007 had a totalof 788 meeting registrations and the attendeesin each category were as follows:

Members 335

Nonmembers 206

Students 19

Accompany Persons 26

Exhibitors 202

The Scientific Program began witheight workshops. Attendees registered for atotal of 794 Workshop Units of ContinuingEducation. On Monday, three Full-day work-shops on Benzodiazepines, Solid Phase Extrac-tion, and Excel Spread Sheet and two Half-dayworkshops on Herbals and Drug FacilitatedCrime were offered. Tuesday’s workshops in-cluded two Full-day workshops on LC/MS andToxicology Jeopardy on DUID and one Half-day workshop on Crossroads of Clinical andForensic Case Interpretations.

Eighty-five posters were presentedduring three sessions within Wednesday andThursday’s schedule of the Scientific Program.Another 30 Platform Presentations were givenas part of the Wednesday - Friday schedule.

Evening events throughout the weekwere designed with S.O.F.T. and North Caro-

lina traditions in mind. The Welcoming Recep-tion, hosted among our more than 200 Exhibitors,had the “down south appeal of North Carolinabarbeque, black-eyed peas and banana pudding”.From here, attendees cozily gathered to enjoy theElmer Gordon Forum before trying their luck atCerilliant’s Nite Owl Reception of Casino tablesand $5K worth of casino tokens. The followingnight was not to be out done as S.O.F.T. attendeeswere taken to an offsite event at the Historic To-bacco Campus in downtown Durham. Attendeeschose to “step” or “triple step” to the Lindy Hopand West Coast Swing hits played by Durham’sown Rebecca and the HiTones or alternativelythey could relax on picnic blankets under themoonlit sky listening to Scott Ainslie, a localblues and jazz musician. Equally enjoyable, thePresident’s Reception boasted a “Surf-n-Turf”meal while artists of the Paperhand Puppet Inter-vention performed for all. After dinner and thetheatrical showcase, attendees with any energy leftwere encouraged to hit the dance floor for a fewmore tunes.

As Saturday came, many attendees werefortunate to find sleep on their agenda; could theybe dreaming about what next year would be likefor S.O.F.T. 2008 in Phoenix?

The S.O.F.T. 2007 Planning Committeewould like to graciously thank all of the exhibi-tors, meeting volunteers and the S.O.F.T. Boardfor their help and support in making this a suc-cessful meeting.

Jeri Ropero Miller & Ruth Winecker: Co-HostsDiana Garside: Events CoordinatorRebecca Jufer Phipps: Scientific ChairWilliam Anderson: Workshop ChairAndrew Mason: Student Enrichment ProgramVickie Watts: S.O.F.T. Meeting CoordinatorLisa O’Dell: S.O.F.T. Exhibit CoordinatorBruce A. Goldberger: S.O.F.T. Web-Master

2 0 0 7 S . O . F. T. A N N U A L M E E T I N G F O C U S E S O N

G R O W T H , E D U C AT I O N I N F O R E N S I C T O X I C O L O G Y ,A N D N O R T H C A R O L I N A T R A D I T I O N S

®

Society of Forensic Toxico logists , Inc .Volume 31, Issue 4

December 2007

TOXTALK

T H A N K Y O U L I S A

After fourteen years of coordinating the exhibiting companies forthe annual meetings, Lisa O’Dell has stepped down as the S.O.F.T. ExhibitorLiaison. Sincere appreciation to Lisa for her thorough collaboration withexhibitors over the years. Lisa would like everyone to know that the relation-ships she has made with the exhibitors, meeting hosts, and attendees will betreasured.

It has been an honor and a privi-lege to serve as the 2007 President of theSociety of Forensic Toxicologists. I’d liketo take this opportunity to thank the mem-bership for allowing me to serve you in thisimportant capacity. I am sincerely apprecia-tive that I have been able to draw upon thevaluable advice and assistance of the entireS.O.F.T. membership, as well as the pastand present members of the S.O.F.T. Boardand Committee Chairs. Indeed, our organi-zation has continued to move forward tomeet the demands of our expanding group.

There has been a great deal of ac-tivity this year, and S.O.F.T. has endeavoredto expand our support of various educa-tional activities in particular. First, I amhappy to report that S.O.F.T has providedfive Education Research Awards and fourYoung Scientist Meeting Awards for thisyear. There are some excellent young de-veloping scientists and researchers workingin our various laboratories! S.O.F.T. is veryfortunate to have the opportunity to supporttheir work. Second, S.O.F.T. was extremelyfortunate to co-sponsor the first S.O.F.T.Student Enrichment Program, where inter-ested high school, college, and graduatestudents were offered the opportunity tolearn more about toxicology in various prac-tice settings. Through the tremendous local-support of Research Triangle Institute, theState Bureau of Investigation, and LabCorp,the students were able to tour local labora-tory facilities, as well as attend didactic lec-tures and discussion with the program’sfaculty. S.O.F.T. plans that this outstandingevent will be continued annually so that wecontinue to cultivate interest in careers inforensic toxicology for the future.

I hope that everyone has had achance to look over the most recent SpecialIssue of the Journal of Analytical Toxicol-ogy. Now in our 27th year of collaborationwith Preston Publications, this issue pre-sents current information on some of themost relevant topics to the practice of foren-sic toxicology. Emerging trends and novelresearch in the areas of analytical, post-mortem and human performance toxicology,as well as case studies of particular interest

to forensic toxicologists, are included inthis valuable resource. On behalf ofS.O.F.T., I would like to thank Dr. SarahKerrigan for accepting the responsibilitiesassociated with serving as Guest Editor ofthis issue. There is a tremendous amountof time and effort involved in creating apublication of high quality, peer-reviewed, scientific papers. This achieve-ment could only be accomplished throughthe combined efforts of Dr. Kerrigan andher dedicated team of volunteer review-ers. This Special Issue of the Journal ofAnalytical Toxicology continues to assistin the dissemination of new informationto practicing forensic toxicologists, aswell as students and trainees.

Along with S.O.F.T.’s continuedgrowth and development, comes both newopportunities and challenging deci-sions. A new ad hoc committee wasformed this past year, comprised ofS.O.F.T. members with financial exper-tise, whose charge was to provide adviceon the development of long-range plan-ning goals and budget for S.O.F.T. Manythanks go to Brad Hepler for agreeing toserve as the first Chair of this committee.As with any new endeavor, there are al-ways unforeseen issues that arise thatrequire more time and effort than origi-nally anticipated. Brad and his committeehave done an outstanding job in definingthe task and beginning to chart a coursefor future financial growth and stabilityfor our growing organization.

The 2007 S.O.F.T. annualmeeting in North Carolina was a hugesuccess! Jeri Miller, Ruth Winecker,and their local team put together an ex-citing scientific program, as well as funsocial activities. Our S.O.F.T. MeetingCoordinator, Vickie Watts, worked tire-lessly, as always, to help organize thesmooth flow of all behind-the-scenesactivities. Lisa O’Dell also continuedher tremendous efforts on our behalf inworking with the many exhibitors at themeeting. The wonderful support of theexhibitors continues to ensure thatS.O.F.T.'s annual meeting continues itstradition of science and fun! Plans arewell underway for S.O.F.T. meetingsthrough 2012. Please visit the SOFTwebsite for more information on thesemeetings as preparations become avail-able.

Finally, as you can see from myreport, it is the combined efforts of themany individuals who volunteer theirtime and talent that makes S.O.F.T. suc-cessful. I am confident that S.O.F.T. willcontinue its strong tradition of fosteringconstructive scientific dialogue, profes-sional development, and educationaloutreach, among our diverse member-ship.

Page 2

PR ES ID EN T’S MES SA GE

BY D I AN A W I LK I NS , PH .D.

Volume 31 , Issue 4

There were 65 different compa-nies that exhibited at and sponsored the2007 S.O.F.T. Annual Meeting in Raleigh,North Carolina. Financial assistance pro-vided by meeting sponsors is essential tomaintaining superior quality and largeparticipation at the meetings. We extendour appreciation for past exhibitor com-mitment and welcome continued alliancewith these exceptional companies.

Agilent TechnologiesAIT Laboratories

Alternative Biomedical SolutionsAmerican Solutions for Business

Applied BiosystemsAxiom Diagnostics, Inc.

Biochemical Diagnostics, Inc.Biotage (Discovery Chemistry)

Branan Medical CorporationBruker Daltonics, Inc.Caliper Life Sciences

Campbell Science CorporationCapitol Vial Brands (Thermo Fisher Scientific)

Cerilliant CorporationChemWare, Inc.

CMI, Inc.Common Cents Systems

Dade Behring, Inc.Data Unlimited International, Inc.

dominick hunter, (Parker-Hannifin Corp.)DPX Labs, LLCEccoTrax, Inc.

Excalibur Lab Specialists, Inc.Express Diagnostics International, Inc.

Forensic MagazineGBF Medical Group

GenTech Scientific, Inc.GERSTEL, Inc.

Immunalysis CorporationInstant Technologies, Inc.

International Diagnostic Systems Corp.

2007 R A L E I G H ME E T I N G E X H I B I T O R S & S P O N S O R S

JEOL USA, Inc.Journal of Analytical Toxicology

JusticeTrax, Inc.Laboratory Corporation of America Holdings

LEAP TechnologiesLin-Zhi International, Inc.

Lipomed, Inc.Microgenics (Thermo Scientific)

MicroLiter Analytical Supplies, Inc.Neogen Corporation

NMS LabsOraSure Technologies, Inc.Orochem Technologies, Inc.

Perkin Elmer Life & Analytical SciencesQuality Assurance Service Corporation

Randox Laboratories, Ltd.Regis TechnologiesRestek Corporation

RocheRTI International

Rudolph Research AnalyticalSciteck, Inc.

SGE Analytical ScienceShamrock Glass Company, Inc.

Shimadzu Scientific Instruments, Inc.

SPEware CorporationStandard Register Co., Lab Solutions Group

Thermo ScientificUnited Chemical Technologies, Inc.

UTAK Laboratories, Inc.Varian, Inc.

Venture Labs, Inc.VertiQ Software, LLC

Waters Corporation

ToxTalk Page 3

symposium of outstanding presenta-tions on various aspects of forensictoxicology practice, given by the pro-gram faculty.

For many students, this wastheir first experience being at a scien-tific conference, and one of our goalswas to make their SOFT-SEP atten-dance reflect that experience. Theyreceived name badges, a folder withschedules, biographies of the present-ers, and other literature, a SOFT-SEPt-shirt, a set of lab glasses, and atten-dance certificates at the conclusion ofthe program. I have had numerousemails and several phone calls fromthe students and their parents andteachers thanking us for presentingthis program, and saying how muchthey or their students appreciated it.We understand that several of the col-lege students have already submittedCV’s to a faculty member, in an effortto secure additional training. One col-lege student told us he drove 1,100miles, from Louisiana, by himself, inorder to attend the program!

Many people worked very hardto put this program together. Specialthanks go to Jeri Miller, one of ourmeeting hosts and the SOFT-SEP Meet-ing Coordinator, to Ruth Winecker, ourother continually supportive MeetingHost, and to Vickie Watts the MeetingCoordinator, Diana Garside, and the restof the local arrangements committee.The presenters, who took time fromtheir busy schedules to prepare and pre-sent their lectures, deserve our thanksalso. They include Catherine Hammet-Stabler, Marilyn Huestis, Marc LeBeau,Robert Middleberg, Jeri Miller, MattSlawson, Peter Stout, Chip Walls, DianaWilkins, and Ruth Winecker. Thanksgo to the laboratories who kindly al-lowed us to visit, including LabCorp,Inc. (Randy Lynn and Phyllis Chan-dler), and the NC-SBI (Jerry Richard-son, Laura Farrin, Hope Copeland).Finally, thanks go to our sponsors, in-cluding LabCorp, Inc., the NC-SBI,NMS Labs, the Research Triangle Insti-tute, and ToxicoLogics, Ltd.

Overall, we are very pleasedwith the reactions,impressions andsuggestions wereceived regardingthe SOFT-SEP.We are hopefulthat the programwill be continuedas a regular partof SOFT’s annualmeeting (planningfor Phoenix hasalready begun!),and we are confi-dent that we havelaid down a goodfoundation onwhich others maybuild in futureyears.

Students and Faculty of the Inaugural SOFT Student Enrichment Program held October 15, 2007 in Raleigh, NC.

By Andrew Mason, S.O.F.T.-SEP 2007 Committee ChairThe inaugural SOFT Student

Enrichment Program (SOFT-SEP) washeld on Monday, October 15, 2007, inconjunction with SOFT’s annual meetingin Raleigh-Durham, NC. Fifty nine of 62accepted High School students attended,while 14 of 15 accepted University orGraduate School students attended, alongwith several other teachers, interestedparents and SOFT members. Total atten-dance was almost 90 individuals, includ-ing the faculty, most of whom attendedthe entire event.

The morning program included alaboratory tour; the High School studentstoured the forensic drug testing lab atLabCorp, Inc., in the Research TrianglePark, while the College students touredthe toxicology and drug chemistry labs atthe NC State Bureau of Investigation(NC-SBI) in Raleigh, NC. The studentsreturned to a provided luncheon that in-cluded table-side discussions with prac-ticing forensic toxicologists. Followinglunch back at the conference site, thestudents were treated to an afternoon

Page 4

FIRST ANNUAL S.O.F.T. STUDENT ENRICHMENT PROGRAM

Volume 31 , Issue 4

ToxTalk Page 5

S.O.F.T 2007 F U N RU N /W A L KA group numbering over 60

strong ran and / or walked a course sur-rounding the Sheraton Imperial HotelThursday morning at dawn during themeeting.

Sincere thanks to Frank Esposito,coordinator of the event, who establishedthe path to follow, recruited partners to

perform as “direction of travel guides”throughout the course, and congratulatedthe athletes upon their return. The FunRun is always a big hit for the fitnesscrowd. All participants received the 2007Fun Run tee shirt and three winners re-ceived a digital heart monitor generouslycontributed by Agilent Technologies.

First Place Men’s Runner:Rob Herndon – time = 20 min. 26 sec.

First Place Women’s Runner:Sue Brown – time = 25 min. 5 sec.

First Place Walker:Eric Muller – time = 42 min. 39 sec.

RE M E M B E R I N G DR . R I E D E R S A N D DR . S U N S H I N E . . .

For the second year, the Rieders/Sunshine Silent Auction has been a success.This is due to the great response from both theS.O.F.T. members and the exhibitors at the an-nual show. At the recent meeting in North Caro-lina, $4,409 was raised. This will be used foreducational venues sponsored by the S.O.F.T.organization. Several people well along in theircareers have made mention the stipends receivedfrom the organization came along just when theyneeded it most.

How better to honor the memory ofthese two great men than to help those studyingthe sciences?

Dr. Irving Sunshine taught so many ofour present day toxicologists. One student thatremembers him fondly is Dr. Brad Hepler. Thefollowing thoughts are his, from an article hewrote a few years ago: Dr. Sunshine was a“first class nudger”. He was both student andteacher, always open to new ideas. Passionateabout his endeavors, Irv had high expectationsfor his students and all those involved in his life.

Dr. Sunshine and his wife, Helen,raised two sons that were well prepared for life.They included the students in their warm circle,indeed, even housing them when the need arose.

Dr. Frederick Rieders informationcomes from his son, Dr. Michael Rieders. Hetells us, “My father came here from Vienna,Austria. One of his first jobs was as a FullerBrush salesman in Harlem. This, among otherthings, shaped his future. He could not acceptthat women and minority people did not haveaccess to education and other life benefits.”

When World War II broke out, heenlisted in the military. Dr. Rieders was verypatriotic. At one point he was actively recruitedby the Communist Party and publicly dis-avowed their cause. His fervor for America ledto later interesting projects for the government.After the war, Dr. Rieders went to college onthe G.I. bill. It was then that he discoveredscience. It became his lifelong work, not only ajob, but an adventure in learning. His business,National Medical Service, has a well deservedfine reputation.

The Dr. Frederick Rieders Foundationcontinues his work educating young people inthe sciences. He wanted them to be excitedabout learning. The foundation has a keen in-terest in females and minorities---a perfect ex-ample of Dr. Rieders memory of his early days.

Now you will read a personal recol-lection from the other end of the spectrum.Your writer came to know both of these greatmen in a different setting than in the laboratory.In 1979 Shamrock Glass was just gettingstarted. I was new to the glass industry, one ofless than a handful of women. One of NationalMedical Services people spoke of a need for aparticular vial. It was not widely available andvery highly priced, causing them to wash andre-use the vial. Shamrock started having theitem manufactured and it started the companyon a new course besides handmade apparatus.A few years ago at a S.O.F.T. meeting someonepointed Dr. Rieders out of the crowd. I ap-proached him, introduced myself and thankedhim for being such a wonderful customer for

over 25 years. He looked at me intently andsuddenly his eyes lit up. “Headspace vials!” heexclaimed. I was flabbergasted. How couldthis man, with the enormous amount of dailytasks, know about this small detail in his labora-tory? I was deeply touched by the rest of ourconversation and cannot speak of it without alump in my throat. Many times over the yearswe have said, “They (National Medial Services)have put shoes on our children’s feet.” This isvery true. His company has always treated thisvendor as well as his employees with respectand kindness.

A small ad was placed in a laboratorypublication in ’79 or ’80 and Dr. Sunshine wasone that responded. He was pleased to find asource for vials with a reasonable price and fastdelivery. This did not change his frugal waysand his students continued to re-use the vials. Istill chuckle with the memory of making a newcontact and them telling me that they onlyneeded caps and stoppers because they re-usedtheir vials. It was a dead giveaway that theperson was one of the “Sunshine Boys”. If youcan believe this, I had the audacity to ask himfor sales leads. (Please remember, I was ratheryoung---and had two children to support). Hepassed numerous names on to me and gener-ously allowed me to use him as a reference.

I added these words of remembranceof both men because they are both just as im-portant to those of us on the fringes of yourgreat good work as they have been to all of you.It has been an honor to have known them insome small way.

Submitted by Bunnie Gallagher of Shamrock Glass Company

Page 6 Volume 31 , Issue 4

Grateful thanks to both Tinsley Preston, III, and H. Chip Walls for supplying this wonderful selection of photographs!

ToxTalk Page 7

Grateful thanks to both Tinsley Preston, III, and H. Chip Walls for supplying this wonderful selection of photographs!

Page 8 Volume 31 , Issue 4

Grateful thanks to both Tinsley Preston, III, and H. Chip Walls for supplying this wonderful selection of photographs!

ToxTalk Page 9

Grateful thanks to both Tinsley Preston, III, and H. Chip Walls for supplying this wonderful selection of photographs!

Page 10 Volume 31 , Issue 4

T R E A S U R E R ’ S R E P O RTSubmitted by Bradford R. Hepler, Ph.D., DABFT, SOFT Treasurer 2007 / 2008

In 2006, S.O.F.T. engaged a new accountant to assist S.O.F.T.with financial reporting:

Martin J. Halloran, CPA, Member—AICPA and NCACPAPark 21 Business Center18525 Statesville Road, Suite D-02Cornelius, NC 28031

At the February 2007 Interim BOD Meeting, a new Ad HocCommittee was formed to provide advice on the development of long-range planning goals and budget for S.O.F.T. for the next five years. Tocomplete this task, the committee visited the new S.O.F.T. Administra-tive Office for the purpose of reviewing available records for recommen-dations on projected budget items.

Also at the February 2007 meeting, the BOD discussed a rec-ommendation noted in the Budget and Audit Committee’s report 1/31/07to conduct an audit of S.O.F.T.’s financial records and an independentlyreviewed financial statement on a bi-annual basis. This review was fa-cilitated by the Long-Term Strategic Planning Committee’s visit toS.O.F.T.’s office in June 2007.

The Compilation Report for S.O.F.T.’s Tax Year 2006 pre-pared by Mr. Halloran is included on page 11. Through his efforts, all

S.O.F.T. income tax filings are now up to date. Mr. Halloran has visitedthe S.O.F.T. Office in Arizona, and has become familiar with the recordsmaintained at that location. Additionally, he has met with the BOD at theNorth Carolina meeting and made appropriate recommendations how theorganization should proceed with documentation and tracking of financialrecords.

Recommendations include returning to the practice of providingannual Compilation Reports to the membership, along with providing adetailed reconciliation of records and report to the membership with thechange of individuals occupying the office of Treasurer. Finally, Mr.Halloran recommended that a Certified Audit by an independent outsideagency at the end of next year, and every seven years thereafter with re-port to the membership upon completion of the audit. These recommen-dations were voted upon and approved by the BOD.

Finally, a Fund Balance Comparison for the year 1993, to theyears 2001-2006 is tabulated on page 11.

The Income and Expenses for the S.O.F.T. main bank accountfrom January to October 31 is tabulated and presented below along withthe current account balances to date.

Treasurer’s Report—S.O.F.T., Inc. Income / Expenses: January through October 31, 2007

NET INCOME (LOSS): 39,923.35

EXPENSES AMOUNTAAFS SOFT BOD Mtg 847.70AAFS SOFT Night 6,379.16AMEX Account Maint. 59.00Analysis Service Charge 59.00Bank Service Charges 106.10BankCard Service Charge 140.19Contract Labor 195.00ERA/YSMA Awards 9,000.00I-Account 39.80Insurance 651.03JAT Meeting Issue 14,850.00Lease SOFT Office 4,545.53Meeting Expenses 11,526.87SOFT CE Seed Money 2,320.80Office Supplies 3,338.79Payroll Expenses 19,303.33Postage / Shipping 354.61Accountant 4,874.30Refunded Payment 8.00Reimbursements Postage 185.01Registration SOFT Logo 308.66Returned Deposit 110.00Shirt / Mug Merchandise 368.65SOFT Logo Items 752.00SOFT Officer/Comm. Exp. 4,850.02Software Programming 5,433.10State of DE - Inc. Required 254.50Telephone 568.40ToxTalk 11,019.48Website 2,999.22

TOTAL EXPENSES 105,448.25

REVENUE AMOUNTAMEX Account 782.39Application Fees (SOFT) 1,775.00Bank Card Account 4,066.34Dues & Subscriptions 54,208.50ERA Donations 758.00Hospices Contonaux 50.00Interest Earned ERA 6,166.95Interest Earned Reserve 1,764.68Late Fees (Dues) 210.00Mailing Labels Provided 500.00Meeting Proceeds 66,032.74Meeting Registration 290.00Mugs/Shirts/Memorabilia 2,007.00Postage Revenue 96.00Reimbursed CE Expenses 2,810.00Silent Auction SSEP 3,779.00ToxTalk Subscription 75.00

TOTAL REVENUE 145,371.60

Current Account Balance (10-31-07) AMOUNT

USBank - Operations Acct. 143,505.67

USBank - ERA Acct. 175,834.70

USBank - Reserve Acct. 52,788.44

ToxTalk Page 11

T R E A S U R E R ’ S R E P O RT C O N T .

Society of Forensic Toxicologists, Inc.Statement of Income

for year ended December 31, 2006Accountant’s Compilation Report

REVENUE AMOUNT

Meetings 455,709.00

Annual Dues 17,117.00

Donations 386.00

ERA Contributions 1,946.00

Interest Income 11,773.00

TOTAL REVENUE 486,931.00

EXPENSES AMOUNT

Accounting & Legal 3,757.00

Administrative Aide 14,866.00

Bank Fees 598.00

Insurance 652.00

ERA Fund Awards 6,000.00

Donations 2,555.00

Printing 3,984.00

SOFT Logo Items 1,913.00

Office Lease 4,634.00

Office Supplies 9,326.00

ToxTalk Expenses 9,535.00

Web Credit Card Fees 16,032.00

AAFS Hospitality 8,314.00

Misc. Expenses 3,540.00

Meeting Expense 398,751.00

TOTAL EXPENSES 484,457.00

NET INCOME (LOSS) 2,474.00

Society of Forensic Toxicologists, Inc.Balance Sheet

December 31, 2006Accountant’s Compilation Report

ASSETS

CURRENT ASSETS AMOUNT

USBank - Operations Acct. 167,342.00

USBank - ERA Acct. 176,385.00

USBank - Reserve Acct. 51,030.00

Wells Fargo Web Acct. 33,368.00

Wells Fargo Web Savings 101.00

Wells Fargo NC Mtg. Acct. 1,297.00

TOTAL CURRENT ASSETS 429,523.00

LIABILITIES & FUND BALANCES

FUND BALANCES AMOUNT

Unrestricted Fund Balances 253,138.00

Restricted Fund Balances 176,385.00

TOTAL FUND BALANCES 429,523.00

Society of Forensic Toxicologists, Inc.Statement of Fund Balance

December 31, 2006Accountant’s Compilation Report

Society of Forensic Toxicologists, Inc.Fund Balance Comparisons

For the years 1993, 2001-2006

Year Assets Outset of Year Assets Year End Change

1993 91,314.00 95,778.00 4,464.00

2001 226,941.00 271,174.00 44,233.00

2002 271,174.00 323,892.00 52,718.00

2003 323,892.00 346,954.00 23,062.00

2004 346,954.00 443,509.00 96,555.00

2005 443,509.00 427,049.00 -16,460.00

2006 427,049.00 429,523.00 2,474.00

Fund Balance as of 12-31-05 427,049.00

Net Income 2,474.00

Fund Balance as of 12-31-06 429,523.00

Submitted by Section Editor, Dwain Fuller, BS, D-FTCB, TC-NRCC

D R U G S I N T H E N E W S

Page 12

Please send interesting “Drugs In The News” to Section Editor, Dwain Fuller atdwain.fuller@med.va.gov

nificant contributing factor to the deathof both adults and children, either alone,or when it is used concomitantly withrespiratory depressant or cardio-depressant agents like heroin.

Diphenhydramine Pharmacology andToxicology

Diphenhydramine is a commonOTC product used for its antihistaminic,anticholinergic, and sleep-inducingproperties. Both diphenhydramine andthe closely- related dimenhydrinate, the8- chlorotheophylline derivative (orsalt) of diphenhydramine, are used toprevent or treat nausea or motion sick-ness. Dimenhydrinate contains 53-55.5% diphenhydramine. However,little work has been done to compare theactivities of 8-chlorotheophylline totheophylline, and there are few data onthe contribution of the 8- chlorotheo-phylline moiety to the toxicity, pharma-cokinetics or pharmacodynamics ofdimenhydrinate (3). However, theo-phylline is known to posses cardiotoxic-ity due primarily to its inhibitory effectson phosphodiesterase (PDE) leading toincreases in intracellular cyclic-AMPlevels and a positive chronotropic effecton the heart (4). Asthmatics receivinghigh dose theophylline or aminophyllinetreatment (plasma concentrations above20 mcg/ml) may experience cardiac ar-rhythmias or seizures. If 8- chlorotheo-phylline posses positive chronotropiceffects on the heart like theophylline,then its combination with diphenhy-dramine should be re-examined and per-haps, reconsidered.

Most toxicologists are aware ofdiphenhydramine’s central effects of

sleepiness, but some may be less ac-quainted with its peripheral pro-arrhythmic affect and cardiotoxicity.Diphenhydramine is an ethanolaminetype of H1 histamine receptor blockerand also posses type 1A (quinidine-like) antiarrhythmic activity (5).Some will recall that almost 20 yearsago, clinical trials with two class 1C(non-quinidine, non-lidocaine) antiar-rhythmic agents, encainide and fle-cainide, were stopped due to in-creased mortality and that the drugswere subsequently removed from themarket due to their pro-arrhythmicproperties (6). Moreover, in mid-October 2007, the Federal Food andDrug Administration moved to pro-hibit the sale and use of many OTCcough and cold preparations designedfor children under 2 years of age, andare currently moving towards expand-ing that ban to children under 6. Un-fortunately, it has been known foryears that antihistamines should notbe used to treat the symptoms of acold because antihistamines inhibitthe movement of cilia in the nasalmucosa and increase mucus retentionin the airways causing even greaterdifficulty with breathing.

How Common is DiphenhydramineToxicity?

According to the AmericanAssociation of Poison Control Cen-ter’s Toxic Exposure SurveillanceSystem (TESS), in 2003 there were28,092 toxic exposures to diphenhy-dramine reported of which 11,355(40.4%) required medical evaluation.Forty-three percent or 12,089 cases

Editor’s Note: “Cheese” heroin iscontinuing to make the news. In thisIssue, Dr. David Benjamin providesfurther insight to the lethality of thismixture.

I was very interested in readingDwain Fuller’s article on Cheese, whichappeared in the Drugs in the News sec-tion of the September 2007 edition ofToxTalk (Volume 31, Issue 3). In addi-tion to pointing out the dangers of thecombined use of heroin, acetaminophen,and diphenhydramine, it also calls intoattention the toxicity of non-prescriptiondrugs, or so called Over-the-Counter(OTC) drugs likediphenhydramine(Benadryl®) andacetaminophen(Tylenol®). Accord-ing to the manufac-turer of ExtraStrength Tylenol® PM (1), the productcontains acetaminophen 500 mg and

diphenhydramine25 mg, as well asa variety of ex-cipients, solubiliz-ers and dyes.There is also a

liquid formulation that contains thesame amounts of active ingredients in a15 ml dose. Since most toxicologist arewell-acquainted with the liver and kid-ney toxicities of acetaminophen and theoccasional myocardial damage withsubendocardial hemorrhage and focalnecrosis that has been reported withacetaminophen overdosage (2), this arti-cle will focus on the cardiotoxicity ofdiphenhydramine, which can be a sig-

Volume 31 , Issue 4

Dr. Benjamin is a consultant in Forensic Toxicology and an Adjunct Assistant Professor at Boston University School of Medicinewhere he teaches Forensic Toxicology in the school’s Biomedical Forensic Sciences Program. (medlaw@doctorbenjamin.com)

C A R D I O T O X I C I T Y O F D I P H E N H Y D R A M I N E ( B E N A D RY L ® )By David M. Benjamin, Ph.D.

ToxTalk

involved children under 6 years of age,of which 6 cases resulted in fatal out-comes. From 1985 – 2002, a review ofthe TESS data indicated 48 deaths inwhich diphenhydramine was the onlydrug ingested. The ages of these pa-tients ranged from 2 months to 86years, and 7 of these patients were 3years of age or younger (7).

Pharmacokinetic Profile of Diphen-hydramine

Diphenhydramine is rapidlyabsorbed with peak blood levelsachieved within 2-3 hours. A single 50mg dose produces peak blood levels of83 ng/ml at 3 hours (8), with suppres-sion of histamine-induced wheals ap-parent at blood levels of 25-50 ng/mland sedation is present above 50 ng/ml.(9) However, children may exhibitparadoxical stimulation, restlessness,hallucinations, and/or seizures fromdoses that are sedating in adults. (10)The bioavailability of an initial singleoral dose is only 42-62% due to “firstpass” hepatic metabolism. Some in-vestigators have suggested that multi-ple doses or toxic doses may be subjectto non-linear kinetics, and this may bedue, in part, to saturation of hepaticCYP enzymes following initial doses,and extensive genetic polymorphism.(9,11,12)

Diphenhydramine is exten-sively bound to plasma proteins up to

99% and has alarge volume ofdistribution from3-7 L/kg. Itsblood-to-plasmaratio is 0.82, andit is accumulatedin brain at alevel of approxi-mately twice thatof blood. (8,9)

Lessthan 4% of an oral dose of diphenhy-dramine is excreted as intact drug (9).Diphenhydramine is oxidatively

deaminated to nordiphenhydramineand dinordiphenhydramine which areprobably excreted as N-glucuronides.The exhaustive demethylation of di-phenhydramine and oxidative deami-nation of the resulting primary amineleads to the formation of dimethyl-phenoxyacetic acid, which is excretedas a glycine or glutamate conjugate(8). The half-life of diphenhydraminevaries greatly from 2.4-9.3 hours (10),probably indicating extensive geneticpolymorphism. In vitro data indicatethat diphenhydramine is metabolizedby the CYP 2D6 pathway (13) like itsstructurally-related tricyclic antide-pressants and related anti-arrhythmicsfleccainide and mexilitine. This dis-covery provides a reason to have greatconcern about diphenhydramine phar-macogenetics and the associated vari-ability in metabolism since there are 5different allelic forms of CYP 2D6,everything from ultra-extensive me-tabolizers (UM) to poor metabolizers(PM) with great variation in metabolicactivity in between, including 5-10%of the Caucasian and 1-4% of otherethnic populations who have de-creased or no 2D6 activity (PM) (12).These are the patients who get no an-algesia from codeine because theycannot de-methylate codeine to mor-phine, or get dysphoric on dextro-methorphan because they can’t me-tabolize it well.

Diphenhydramine & CardiotoxicityCardiology 101 for Forensic Toxi-cologists (14)

The heart has a natural intrin-sic pacemaker, the sinus node (orsino-atrial (SA) node), that regulatescardiac rate and ensures automaticity.The impulses are carried on a set ofrailroad track-like neutral circuits (theHis-Purkinje System) which spreadthe electrical impulses from the sinusnode through the atria to the atrial-ventricular node (AV node) and thenthroughout the ventricles to coordi-nate the rhythm of the heart. Such

regulation couples the heart’s electri-cally propagated impulses to heart mus-cle to ensure a forceful and efficientmilking of the ventricles during systole.When the intrinsic activity of the heartis disrupted by drugs or disease,changes in normal cardiac pacing canoccur, arrhythmias may develop, or car-diac muscle may lose its ability to force-fully contract. All of these outcomesmean decreased perfusion to the heartitself and all the other organs. Since theheart supplies its own blood via thecoronary arteries during diastole, car-diac dysfunction is a “negative spiral”which leads to increased cardiac dys-function.

If you recall basic cardiac elec-trophysiology, you will remember thatthe electrocardiogram (ECG) representsonly the electrical activity of the heartand does not reflect the resultant muscu-lar activity involved with ventricularsystole and the actual work involved inpumping blood. While I certainly amnot a cardiologist, we all should besomewhat familiar with the interpreta-tion of the standard Lead II ECG and itsrelationship to myocardial physiology,cardiac output and the cardiotoxicity ofdrugs. Cardiac output is defined as theproduct of Heart Rate and the StrokeVolume (also known as the ejectionfraction) and can be written as: CO=HRx SV; stroke volume is the volume ofblood ejected from the left ventricle intothe aorta with each systole (45-60 ml).The CO of the right ventricle may beless than the left ventricle. With in-creases in HR up to 120 or a littlehigher, the SV increases and additionalblood is supplied to the organs. Thisallows us to exercise, walk stairs or oth-erwise exert ourselves and still maintainoxygenation of highly metabolic mus-cles and organs. But after the HR getstoo high, CO decreases and so does per-fusion. This is why tachycardia(HR>100 bpm; tachyarrhythmias) pre-sent a health danger. Decreased perfu-sion of the heart and brain can causefainting (syncope) strokes (CVAs), and

Page 13

D R U G S I N T H E N E W S ( C O N T I N U E D )

DiphenhydramineChemical Structure

D R U G S I N T H E N E W S ( C O N T I N U E D )

nous and the heart does not pumpblood as effectively as it does with anormal rhythm. Less efficient pump-ing leads to decreases in cardiac out-put, decreased perfusion of cardiacmuscle and secondary tissue hypoxia.Once the heart becomes hypoxic, itsfunction further deteriorates and soonpaCO2 (arterial CO2 concentration)increases and the patient develops res-piratory acidosis. As bicarbonate isshifted to compensate for the respira-tory acidosis, the patient develops asuperimposed metabolic acidosis.When the heart suffers an increasedperiod of hypoxia and acidosis, it be-comes more irritable and even moreserious arrhythmias occur, until theheart begins to fibrillate (uncoordin-ated muscular movement which is inef-fective in pumping blood) and ulti-mately stops. Acidosis must be cor-rected with bicarbonate administrationbefore the heart can be defibrillatedeffectively, and coincidently, sodiumbicarbonate also treats arrhythmiascaused by class IA local anestheticagents including diphenhydramine(15).

Antihistamines Share a History ofCardiotoxicity

Initially, cardiotoxicity of anti-histamines was probably ascribed tothe anticholinergic effects whichblocked the vagal input to the heart andcaused tachycardia. However, by 1998the first two non-sedating antihista-mines, terfenadine (Seldane®) andastemizole (Hismanal®) were found tocause long QT syndrome and torsadesde pointes when their metabolism wasblocked by CYP 3A4 inhibitors like“azole” antifungal agents and erythro-mycin-like macrolide antibiotics, andthe FDA had to ask the manufacturersto remove the drugs from the marketplace (16). Since then, diphenhy-dramine has been found to cause toras-des de pointes (17) and widened QRScomplexes and prolonged QT intervals(18). Another investigator reported a

case of moderate diphenhydramineoverdose (625 mg) with concomitantacetaminophen ingestion which led toprolonged QT intervals and abnormalT waves (19). In 1998, Karch sug-gested that patients with cardio-megaly or myocardial fibrosis may beat additional risk of cardiotoxicityfrom diphenhydramine (20).

SummaryDiphenhydramine is an etha-

nolamine type of H1 histamine recep-tor blocker which posses type 1A(quinidine-like) antiarrhythmic activ-ity and is metabolized by the CYP2D6 cytochrome which is subject togreat polymorphism and inter-subjectvariability. Children with poorly de-veloped microsomal enzyme systemsand adults with impaired or absentisoforms of CYP 2D6 would have anintrinsic sensitivity to the pro-arrhythmic cardiotoxic effects of di-phenhydramine, even without theconcomitant exposure to a cardiode-pressant drug like heroin.

Recent regulatory interven-tion by the Federal Food and DrugAdministration to restrict the use ofcough and cold preparations contain-ing agents like diphenhydramine,dextromethorphan and phenethyl-amine decongestants in children un-der 6 years of age was long overdueand should reduce the number of pe-diatric hospitalizations for diphenhy-dramine toxicity and other OTC drug-induced pediatric mishaps reported inthe clinical toxicology literature.Moreover, as described by DwainFuller in his article on “Cheese” inthe last edition of ToxTalk, diphenhy-dramine and possibly acetaminophenmay contribute to the deaths of count-less individuals who combine thesedrugs with heroin and “snort” themixture in order to intensify theeuphoric effect. Unfortunately, whilerecreational drug users may think thatthey are using a safer combination byadding diphenhydramine to the

Oxycodone—

heart attacks(myocardial in-farctions; MIs).The same canoccur when theHR slows downtoo much(bradycardia;HR<60). Theorchestration ofthe cardiac cir-cuitry can bemonitoredthrough its elec-trical activity bythe electrocar-diogram (ECG).

You will recall that the P waverepresents atrial depolarization and thatthe QRS complex represents ventricu-lar depolarization and the T waverepresents ventricular repolarization.The ECG is recorded on graph paper.The time graduations on the X Axis are1 mm apart with every fifth line dark-ened. Standard paper speed is 25 mm/sthus each mm = 0.04 s and 5 mm =0.20 s. From the width of these waves,the duration of each wave of the ECGcan be measured, and cardiac pacingmonitored. The vertical axis measuresvoltage amplitude.

Cardiotoxicity of Pro-arrhythmicDrugs

The classical type 1A antiar-rhythmic agent is quinidine. Quinidineis known for causing a widening of theQRS complex (i.e., takes more time forventricular repolarization to occur) (5).This is due to the local anesthetic ef-fect of class IA agents on the electricalconduction fibers of the heart. As aresult, the conduction velocity of theelectrical impulse originating in thesinus node of the heart is slowed andan abnormal rhythm develops. Whenthe electrical rhythm of the heart be-comes abnormal, the electromechanicalrelationship between rhythm and car-diac pumping also becomes asynchro-

Page 14 Volume 31 , Issue 4

D R U G S I N T H E N E W S ( C O N T I N U E D )mixture and using less heroin, they areactually trading a decrease in the respira-tory depressant effects of the heroin for apotentiation of the cardiotoxicity.

When you consider the lack ofinformation about the percent of heroinin street drugs, the great inter-subjectvariability in the metabolism of diphen-hydramine, and vast number of unknown“cutting agents” used in street drugs, it isno wonder that “Cheese” has become amajor public health danger and thatteenaged youths have been among thethose most often afflicted. It is clear thatbetter drug abuse education must be of-fered to elementary and secondaryschool students, and that existing pro-grams have failed. Since we can’t put apharmacologist or toxicologist into everyhousehold, maybe we can put one intoevery school. Educators, parents, toxi-cologists and local poison control centersshould work together to develop bettereducational programs on drugs of abuse,and present them to parents and studentsas soon as students enter school. Afterall, you only get one chance to make agood first impression, and one time maybe all it takes. Just ask Bostonians, theBoston Celtics Basketball team, and thefamily of Len Bias!

References

1. McNeil Consumer Products,Package Insert for Extra StrengthTylenol PM. Physicians Desk Refer-ence, Thompson PDR, p 1875 (2007)

2. N.G. Sanerkin. Acute MyocardialNecrosis in Paracetamol Poisoning.Br. Med. J. 3: 478 (1971)

3. E.J. Scharman, A.R. Erdman,P.J. Wax, et al.Diphenhydramine andDimenhydrinate Poisoning: anEvidence-Based ConsensusGuideline for Out-of-HospitalManagement. Clin. Tox. 44:205-223 (2006)

4. Goodman and Gilman’s ThePharmacological Basis of Thera-peutics. Hardman and Limmbird,Eds. 3rd Ed., McGraw-Hill,p 674 (1996)

5. L.H. Opie, IV. AntiarrhythmicAgents. Lancet. pp 861-867,April 19, 1980

6. The Cardiac Arrest SuppressionTrial (CAST) Investigators.NEJM 321: 406-413 (1989)

7. W.A. Watson, T.L. Litovitz, W.Klein-Schwartz, et al. 2003Annual Report of the AmericanAssociation of Poison ControlCenters Toxic Exposure Surveil-lance System. Am. J. Emerg.Med. 22: 335-404 (2004)

8. R.C. Baselt. Disposition of Drugsand Toxic Chemicals in Man. 5thEd. Chemical Toxicology Insti-tute pp 289-292, (2000)

9. F. Bochner, G. Carruthers, J.Kampmann, et al. Handbook ofClinical Pharmacology. 2nd Ed.Little, Brown and Company, pp178-179 (1983)

10. AHSF Drug Information.American Society of Health-System Pharmacists, pp 16-18(2006)

11. B. Ekwall, B. Ekwall, and C.Clemedson. Time-released Le-thal Blood Concentrations fromAcute Human Poisonings ofChemicals, Part 2: The Mono-graphs No. 62, Diphenhy-dramine. 1st Internet Ed. (2001)(www.expertradet.se)

12. T.C. Kupiec, V. Raj and N. Vu.Pharmacogenomics for the Foren-sic Toxicologist. J. Analyt. Toxi-col. 30: 65-72 (2006)

13. B.A. Hamelin, A. Bouyad, B. Dro-let, et al. In Vitro Characterizationof Cytochrome P450 2D6 Inhibi-tion by Classic H1 Histamine Re-ceptor Antagonists. Drug Metab.Disp. 26: 536-539 (1998)

14. Harrison’s Principles of InternalMedicine. Braunwald,Isselbacher, Petersdorf,Wilson, Martin and Fauci, Eds.pp 916-920 (1987)

15. A.N. Sharma, A.H. Hexdall, E.K.Chang, et al. Diphenhydramine-induced Wide Complex Dysrhyth-mia Responds to Treatment WithSodium Bicarbonate. Am. J.Emerg. Med. 21: 212-215 (2003)

16. M.J. Cupp and T.S. Tracy. Cyto-chrome P450: New Nomenclatureand Clinical Implications. Am.Fam. Physician 57: 107-116(1998)

17. A.K. Joshi, T. Sljapic, H. Borghei,et al. Case of Polymorphic Ven-tricular Tachycardia in Diphenhy-dramine Poisoning. J. Cardio-vasc. Electrophysiol. 15: 591-593(2004)

18. A.C. Thakur, A.K. Aslam, A.F.Aslam, et al. QT Interval Prolon-gation in Diphenhydramine Toxic-ity. Int. J. Cardiol. 98: 341-343(2005)

19. J.W. Sype and I.A. Khan. Pro-longed QT Interval with MarkedAbnormal Ventricular Repolariza-tion in Diphenhydramine Over-dose. Int. J. Cardiol. 99: 333-335(2005)

20. S.B. Karch. DiphenhydramineToxicity: Comparison of Postmor-tem Findings in Diphenhy-dramine-, Cocaine-, and Heroin-related deaths. Am. J. Forensic

“Cheese”, apotentiallylethal drugmixture ofheroin andTylenol PM,usuallysnorted andinexpensiveto obtain isappealing toteens.

ToxTalk Page 15

Submitted by Section Editor, Matthew Barnhill, Ph.D.

Please send interesting “Case Notes” to Section Editor, Matthew Barnhill, Ph.D.at mbarnhilljr@worldnet.att.net

C A S E N O T E S : # 1 T W O M I RTA Z A P I N E R E L AT E D F ATA L I T I E SaC.J. House, aL.Y. Gorczynski, bG.R. Jones

a. Centre of Forensic Sciences, Toxicology, Toronto, Ontario, M7A 2G8

b. Office of the Chief Medical Examiner, Chief Toxicologist, Edmonton, Alberta, T6H 5R8

Mirtazapine is a tetracyclicpiperazinoazepine structurally relatedto mianserine but unrelated to othertricyclic antidepressants or selectiveserotonin reuptake inhibitors (SSRIs).In Canada, mirtazapine is indicatedfor the treatment of depression and inparticular, patients suffering from ma-jor depressive disorder. Mirtazapinehas demonstrated both noradrenergicand serotonergic effects in vitro andin animal models. There is no evi-dence of significant serotonergic ef-fects in humans and recent reviewshave reported little or no evidence ofserotonergic activity even in over-dose. Mirtazapine is readily absorbedfollowing oral administration andgenerally individuals reach plasmaconcentrations not exceeding 0.10mg/L following a single oral dose.During steady state, Cmax and troughplasma concentrations of mirtazapinerarely exceed 0.18 mg/L and 0.08 mg/L, respectively2,. Mirtazapine hasbeen reported as an incidental findingpost-mortem at concentrations as highas 0.57 mg/L centrally and 0.44 mg/Lperipherally.

Reports of significant toxicityfollowing overdose by mirtazapinealone is rare. Common adverse ef-fects of mirtazapine include drowsi-ness, dizziness, increased appetite andweight gain, and in some cases mildtachycardia. Despite increased re-ports of sedation and drowsiness ascompared to placebo, these effects aremild in comparison to some tricyclicantidepressants. Demonstrating its

margin of safety in overdose, threecases have been described with individ-ual plasma concentrations of 2.3 mg/Lat admission, 0.48 mg/L 20 hrs afteringestion and 0.37 mg/L approximately41 hours after ingestion. The first twopatients exhibited varying degrees ofsomnolence and in one case mild sinustachycardia was also described,.

Mirtazapine has been impli-cated in few deaths as a single intoxi-cant but is routinely detected in cases ofpolypharmacy1. Its interaction in casesof polypharmacy is often unclear, how-ever, mirtazapine is neither a potent in-hibitor nor inducer of common P450isoenzymes. In six cases where mirta-zapine was the sole intoxicant, the me-dian, 10th and 90th percentile femoralblood concentrations were 2.3 mg/L, 1.0and 4.3 mg/L, respectively. In a seriesof mixed drug intoxications, concentra-tions ranged from 0.38 to 2.3 mg/L insamples of central blood and peripher-ally from 0.45 to 3.4 mg/L5,. Mirtazap-ine has often demonstrated post-mortemconcentration differences resulting incentral to peripheral ratios (C/P) rangingfrom 0.6 to 1.71. In a series of ninecases the mean and median C/P were1.2 and 1.33, respectively4.

We present two additional caseswith evidence of significant mirtazapineoverdose. Central and peripheral wholeblood concentrations of mirtazapinewere determined along with a compre-hensive toxicological screening of rele-vant samples. Samples were examinedby screening procedures for the pres-ence of volatiles, therapeutics and illicit

drugs as described elsewhere. Mirta-zapine was detected during generalscreening procedures at the Centre ofForensic Sciences, Ontario and quan-titated by gas chromatography withnitrogen phosphorus detection (GC-NPD) at the Office of the Chief Medi-cal Examiner, Alberta. Briefly, blood(1 mL) was extracted by a 1-chlorobutane liquid-liquid acid back-extraction procedure. Following ex-traction, samples were dried and re-constituted in 100 μL 1-chlorobutane.A 2 mL aliquot was analyzed by GC-NPD (Agilent 5890 or 6890, HP-5, 10m x 0.32 mm x 1 mm film capillarycolumn). Amitriptyline was used asthe internal standard. Calibratorswere prepared by spiking mirtazapineinto blank blood to establish concen-trations of 0.05, 0.1, 0.25, 0.5, 1.0, 2.0and 5.0 mg/L. The results of all cali-brators were within ±20% of targetwith correlation of >0.99. An inde-pendently prepared positive controlhaving a nominal value of 0.54 mg/Lwas included with each run. Methodperformance was based on positivecontrol values over a 30-month period(mean (SD) 0.578 ± 0.046 mg/L, 8.1%CV, n=14).

Case 1: A 46-year-old malewas found dead at home. He had apast medical history of depression andbipolar disorder with reported previ-ous suicide attempts. Empty prescrip-tion containers for venlafaxine, olan-zapine, lorazepam, mirtazapine andvalproic acid were found nearby. Atautopsy, particulate matter consistent

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Volume 31 , Issue 4

with tablet debris was found in thestomach contents and small bowel, andno cause of death was determined.

Case 2: A 72-year-old femalewas found dead in her locked apartment.She had a past medical history of de-pression with reports of previous suicideattempts by alcohol and drug overdose.The patient was prescribed lorazepamand mirtazapine and she was reportedlytaking acetaminophen. Post-mortemexamination revealed pulmonaryedema. There were no external or inter-nal injuries or natural disease that couldaccount for death.

We present two of the highestconcentrations of mirtazapine reportedto date. The concentrations are consis-tent with toxicity due to mirtazapineoverdose. In the first case, mixed drugtoxicity is probable as elevatednoradrenergic effects due to venlafaxineand additive sedation due to lorazepamwas likely present. The second casesimilarly reflects toxicity due to the ef-fects of mirtazapine. These effects mayhave been influenced by the elevatedblood alcohol concentration. Some de-composition was present in the urinesample in this case, raising the possibil-ity that some of the alcohol could havebeen formed by post-mortem neoforma-tion. However, the presence of an ele-vated ethanol concentration in theblood, which lacked indication of putre-faction, confirms that alcohol was in-gested prior to death.

The C/P in these two cases isgreater than the average C/P previouslyreported. In these two cases the heart tofemoral blood ratios were 1.5 and 2.2.Incomplete distribution of mirtazapinefollowing a large overdose could havecontributed to the higher ratios. Giventhe propensity for increases in post-mortem concentrations of centrally col-lected samples due to these redistribu-tion artefacts, especially in cases fol-lowing oral overdose, peripherally col-lected samples are recommended forpost-mortem toxicological testing.

References

1. W.S. Waring, A.M.Good, and D.N.Bateman. Lack of significant toxicityafter mirtazapine overdose: a five-year review of cases admitted to aregional toxicology unit. Clin. Toxi-col. 45: 45-50 (2007)

2. C.J. Timmer, J.M. Sitsen, and L.P. Del-bressine. Clinical pharmacokineticsof mirtazapine. Clin. Pharmacokinet.38(6): 461-474 (2000)

3. M. Reis, J. Prochazka, A. Sitsen, J.Ahlner, and F. Bengtsson. Inter- andintraindividual pharmacokineticvariations of mirtazapine and its n-demethyl metabolite in patientstreated for major depressive disorder.A 6-month therapeutic drug monitor-ing study. Ther. Drug Minot. 27(4):469-477 (2005)

4. D.T. Anderson, K.L. Fritz, and J.J.Muto. Distribution of mirtazapine(Remeron®) in thirteen post-mortemcases. J. Anal. Toxicol. 23: 544-548(1999)

5. C. Kirkton and I.M. McIntyre. Thera-peutic and toxic concentrations ofmirtazapine. J. Anal. Toxicol. 30:687-691 (2006)

6. J. Fawcett and R.L. Barkin. Review ofthe results from clinical studies on theefficacy, safety and tolerability of mir-tazapine for the treatment of patientswith major depression. J. Affect. Dis.51: 267-285 (1998)

7. R. Holzbach, H. Jahn, F.-G. Pajonk, andC. Mähne. Suicide attempts with mir-tazapine overdose without complica-tions. Biol. Psych. 44: 925-926 (1998)

8. W. Retz, S. Maier, F. Maris, and M.Rösler. Non-fatal mirtazapine over-dose. Int. Clin. Psychopharmacol.13: 277-279 (1998)

9. M. Reis, T. Aamo, J. Ahlner, and H.Druid. Reference concentrations ofantidepressants. A compilation ofpost-mortem and therapeutic levels.J. Anal. Toxicol. 31: 254-264 (2007)

10. S. Wenzel, R. Aderjan, R. Mattern, I.Pedal, and G. Skopp. Tissue distribu-tion of mirtazapine and desmethylmir-tazapine in a case of mirtazapine poi-soning. Forensic Sci. Int. 156: 229-236 (2006)

Table 1: Results toxicological testing (units are mg/L unless otherwise indicated).

*Evidence of putrefaction

Case 1 Femoral Blood Heart Blood Urine

Mirtazapine 4.5 6.8

Venlafaxine 2.8

Lorazepam 0.28

Valproic acid 60

Olanzapine <0.13

Acetone 4 mg/dL

Case 2 Femoral Blood Heart Blood Urine

Mirtazapine 5.5 12

Lorazepam 0.027

Ethanol 136 mg/dL 171 mg/L*

ToxTalk Page 17

C A S E N O T E S # 1 ( C O N T I N U E D )

Page 18 Volume 31, Issue 4

F A L L 2 0 0 7 S . O . F. T. M E M B E R S H I P S U RV E Y : A N N U A L M E E T I N G

F E E D B A C K A N D C U R R E N T C O N T I N U I N G E D U C AT I O N N E E D S

Submitted by Jeri Ropero-Miller, Ph.D. and Peter Stout, Ph.D.

SO- SOFT ADVE NT URES

Significant Others of S.O.F.T.Members (SO-SOFT) see to it that theyexplore around the many S.O.F.T. meet-ing destinations. While in the Raleigh /Durham/ Chapel Hill area the group jour-neyed to Seagrove visiting various pottersand shopped. While there, they stoppedat the local Jug Town Café to partake in aBlue Plate Special.

After the annual meeting thisOctober, S.O.F.T. with the help of RTIInternational polled their membership toassess their educational experience at theannual meeting and to determine the cur-rent continuing educational needs forplanning future educational opportunitiesfor SOFT sponsorship. A broadcast elec-tronic invitation was sent in late Octoberto over eight hundred SOFT members,with one reminder email sent the follow-ing week. All members were asked toparticipate regardless of whether or notthey attended the 2007 Annual meeting.

The response rate for this surveyapproached 35%. Of the 283 responders,71% of responders (200 members) didattend the annual meeting. The distribu-tion of position was fairly even acrosscategories from chemist to director. Thosewho could not attend the meeting ex-plained that inadequate funding (53%),schedule conflicts (35%), or inadequatepersonnel resources (23%) were the pri-mary reasons they could not attend.

Most meeting attendees foundthe on-line registration easy to follow,appropriately available during the year,and added value to the meeting registra-tion process (>90% rated all three criteriaas ‘good’ or ‘excellent’). The overall qual-ity of the scientific platforms and postersessions (room quality, room temperature,sound quality, visual quality, organizationof the scientific program, speaker effec-tiveness, content usefulness) were rated‘good’ to ‘excellent’, with greater than90% of the meeting attendees being com-pletely satisfied. The room temperature(excellent + good rating: 80%) and useful-ness of the content (excellent + good rat-ing: 88%) were the lowest ranking evalu-

ated categories. Reported strengths of theworkshops included “high quality contentand presentation”, but attendees felt theroom size for the posters while improvedby the addition of a second room, still wascramped and loud at times.

For meeting attendees, 80% tookat least one continuing education work-shop (28% with 1 workshop), but mostregistered for two or three workshops(61% and 12%, respectively). The overallquality of the workshops (room quality,room temperature, sound quality, visualquality, handout quality, speaker effec-tiveness, content usefulness) were rated‘good’ to ‘excellent’, with greater than90% of workshop attendees being satis-fied with the room and visual qualitywhile the lowest rating was afforded toroom temperature (excellent + good rat-ing: 78%). Reported strengths of theworkshops included “high quality contentand presentation”, but attendees felt thatthe “readability” of the workshop hand-outs could be improved.

For the overall meeting evalua-tion quality of the meeting (room quality,room temperature, sound quality, visualquality, handout quality, speaker effec-tiveness, content usefulness) were rated‘good’ to ‘excellent’, with greater than90% of workshop attendees being satis-fied with the room, visual quality, organi-zation of scientific program, and speakereffectiveness. 89% of respondents ratedthe usefulness of the content as “good” or“excellent” while the lowest ratings wereafforded to room temperature (excellent +good rating: 79%) and sound quality(excellent + good rating: 83%). Reportedstrengths of the meeting included “highquality content and presentations”. Re-

spondents repeatedly mentioned that theposter sessions were cramped and difficultto navigate.

For future planning and continu-ing education, 70% of respondents saidthey or others in their institution have aneed for continuing education. The topranked needs for future continuing educa-tion that would be applicable to all person-nel were LC/MS/MS basic theory, specificdrug issues, and QA/QC practices. Thesewere followed by GC/MS basic theory,solid phase extraction theory and practicallaboratory solution. Basic laboratory tech-niques, basic laboratory documentationand alcohol analysis were the third mostcommon priority.

For more advanced topics pertain-ing to more “senior” personnel, drug spe-cific interpretation was the most highlyprioritized topic of all subjects polled fol-lowed by advanced LC/MS/MS theory andexpert testimony topics. QA/QC manage-ment, regulatory issues, practical labora-tory solutions and neurocognitive testoverview were most commonly ranked assecond priority and herbal drug issues andpharmacogenomics were ranked third.Generally, the advanced topics were allranked higher priorities than the topicspertinent to all personnel. This is perhapsreflective that those attending SOFT tendto be more senior personnel.

Thank you to all who took time tocomplete the survey; your input is veryvaluable to planning future meetings. Spe-cific information is helpful to planningcommittees establishing the next severalyears of SOFT meetings. We look forwardto seeing everyone at future SOFT meet-ings and hope to continue to improve thevalue of SOFT meetings for all attendees.

Other days smallergroups went to the DukeChapel, Sarah P. DukeGardens of Chapel Hill andof course the mall. Theselovely ladies are also regular,dependable volunteers at theregistration desk year afteryear. Much thanks to you all.

Tox Talk Page 19

AB FT N E W SAmerican Board of Forensic Toxicology, Inc. (www.abft.org)

ABFT is accredited by the Forensic Specialities Accreditation Board

ABFT President: Yale H. Caplan, Ph.D., DABFT

WHAT A GUY!

Special thanks to S. Tinsley Pre-ston, III of Preston Publicationsfor his continued supporting rolein providing the Journal of Analytical Toxicology SpecialIssue to all meeting attendees. Tinsley also donated an an-nual subscription of JAT to the Sunshine/Rieders SilentAuction event valued over $500. In addition to his afore-mentioned generosity, Tinsley is also an accomplished pho-tographer and has kindly contributed his photographs takenin NC for use in the ToxTalk publications. Thank you forall you do!

PHOTO CREDITS:

Chip Walls, long time and beloved S.O.F.T. member, also atalented photographer, has generously supplied copies ofthe hundreds of photographs he took at the 2007 Raleighmeeting for all to enjoy. Sincere appreciation to you Chip.

DUES TIME

Enclosed with this issue is your2008 S.O.F.T. Annual Dues Notice. Pleasepay dues before the January 31 deadline.There are three ways to pay:

charge on-line via the website, or mail in the dues form with a check, or mail in the dues form with your charge

number written in.

The next issue (March) of Tox-Talk will include your 2008 S.O.F.T.Membership Directory.

It is the responsibility of eachS.O.F.T. member to keep the office in-formed of any change address and/orchanges in contact information.

The ABFT fee waiver program, that endedon December 31, 2006 was a tremendoussuccess with 66 new applicants now goingthrough the certification process. Currentlythere are 162 active Certificants (121 Dip-lomates and 41 Forensic Toxicology Spe-cialists) and 33 Emeritus Diplomates.

Congratulations New Certificants:

Laura LeBay, DABFT

Laureen Marinetti, DABFT

Julia Pearson, DABFT

Eric Alexy, FTSABFT

Myron Gebhardt, FTSABFT

Mattheu Miller, FTSABFT

Douglas Smith, FTSABFT

Michael Wagner, FTSABFT

Gregory Zavatsky, FTSABFT

Certification Now Open Internationally:ABFT certification, originally limited tothe United States and Canada, has beenextended internationally. This is in re-sponse to the many requests for certifica-tion from non-U.S. citizens around theworld. The only restrictions are that theexamination must be taken in English andtaken in the United States at our desig-nated examination sites. Candidate’s edu-cation must be documented by interna-tionally recognized organizations. Ques-tions may be sent by email to abftox.com

M E M B E R N E W S

PL AN TO V I S IT PH OE NI X I N 2008Big plans are underway to make

the 2008 Phoenix meeting memorable andfun. The planning committee is currentlybusy putting together an all encompassinggreat scientific program. With this issue ofToxTalk, you will find a three page Work-shop Proposal, a Call for Papers for the JAT2008 Special Issue, and the PreliminaryProgram for use in planning your stay.Reservations at the hotel will be availableafter January 1, 2008. The Pointe SouthMountain has just underwent a multi-million dollar renovation and a namechange to The Arizona Grand Hotel. The

S.O.F.T. special room rate is $189.Every room is a two room suite, perfectto bring the family for an October get-away.

The Exhibit Hall at this ArizonaGrand Hotel is 20,000 square feet,roomy enough to display the poster ses-sions within, and will be the site of allreceptions. All events will take place onsite. It is highly recommended that plansbe made to stay at the meeting hotel .The two room suite is perfect for sharingif the room rate is too high. for govern-ment employees. October in Phoenix is

a premier travel destination when ratesare highest. This resort features a waterpark, an 18 hole golf course, lighted ten-nis courts, biking, hiking, horseback rid-ing, spa services, six unique on-site res-taurants, and more.

For those who want to extendyour stay into a family vacation, there aremany destination tours available to theGrand Canyon, Sedona, etc.

After March 1, the on-line regis-tration will be up and operable for atten-dee registration and workshop sign-ups..

Future S.O.F.T. Meeting Info

2008: Phoenix, AZ……………....Oct. 27-31, 2008………………….Vickie Watts, Norman Wade

2009: Oklahoma City, OK………Oct. 18-23, 2009…………………...………………...Phil Kemp

2010: Richmond, VA…………………………….……………..Michelle Peace, Lisa Tarnai Moak

2011: San Francisco, CA…………………………………………..…..……………Nikolas Lemos

2012: Boston, MA……………………………………...………………….………Michael Wagner

S . O . F. T. 2 0 0 8 : P H O E N I X , A R I Z O N A

2 0 0 8 S . O . F. T. O F F I C E R S & C O M M I T T E E C H A I R S

Committee Committee ChairNominating……………………………………Diana Wilkins, Ph.D.Membership………………………. ………….Sarah Kerrigan, Ph.D.Strategic Planning……………………………..Bradford Hepler, Ph.D., DABFTBudget, Finance, and Audit…………………...Robert Turk, Ph.D., DABFTToxTalk Co-Editors…………………………...Yale Caplan, Ph.D., DABFT

Vickie Watts, M.S.ByLaws………………………………………..Yale Caplan, Ph.D., DABFTPublications (JAT Special Issue) ……………..Dan Anderson, M.S., ABFTAwards...………………………………………Philip Kemp, Ph.D., DABFTDrugs & Driving………………………………Sarah Kerrigan, Ph.D.Meeting Resource……………………………..Anthony Costantino, Ph.D., DABFTPolicy and Procedure………………………….William Anderson, Ph.D.SOFT Internet Web-Site………………………Bruce Goldberger, Ph.D., DABFTContinuing Education…………………………Ann Marie Gordon, M.S.Laboratory Guidelines………………………...W. Lee Hearn, Ph,D.Ethics………………………………………….Aaron Jacobs, Ph.D.Drug Facilitated Rape & Sexual Assault……...Marc LeBeau, Ph.D.MS/MS Guidelines……….…………………...John Cody, Ph.D.

ToxTalk Deadlines for Contributions:

February 1 for March Issue

May 1 for June Issue

August 1 for September Issue

November 1 for December Issue

®

Article layout, digital mechanics, grammaticalediting, and graphic assistance for ToxTalkprovided by volunteer students, David Wattsand Kayla Fulmer.

President - Christine Moore, Ph.D., DABCCV. Pres. - Anthony Costantino, Ph.D.,DABFTSecretary - Sarah Kerrigan, Ph.D.Treasurer - Bradford Hepler, Ph.D., DABFT

Directors -Ashraf Mozayani, Ph.D., DABFTMarc LeBeau, Ph.D.Peter Stout, Ph.D., DABFTDan Anderson, M.S., ABFTDwain Fuller, B.S., DFTCB

Any S.O.F.T. member interested inserving on a committee should contact theS.O.F.T. President or the Committee Chair.

Above: Downtown Phoenix viewed from South Mountain.Upper Right: Phoenix is a valley surrounded by mountains.Right: Visitors may tour the 8,000 sq. ft. Mystery Mansion

built into the base of South Mountain.

S.O.F.T. Administrative OfficeOne Macdonald Center1 N. Macdonald St., Suite 15Mesa, AZ 85201

Phone: 888-866-SOFT (7638)Fax: 480-839-9106E-mail: ToxTalk@soft-tox.org

Office@soft-tox.org

Society of ForensicTox icolog ists , Inc.

ToxTalk is the official publication of the Society of Forensic Toxicologists, Inc., mailedquarterly (bulk mail) to its members. It is each member’s responsibility to report changesof address to the SOFT Administrative Office. Non-members may receive ToxTalk for $15per calendar year. Checks payable to SOFT may be mailed to the SOFT AdministrativeOffice. To submit articles or address ToxTalk issues please email to ToxTalk@soft-tox.org.

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