Rapid Enantiomeric Separation of Basic Drugs and Metabolites:A Universal Strategy for Ultra-Fast Method Development.

John C. Hudson and Hans A. Dewald, Beckman Coulter, Inc., Fullerton, CA, USA

IntroductionIntroduction

This work describes the use of charged cyclodextrins in a continuing search for a universal strategy for separation of enantiomeric drug substances. The use of highly sulfated cyclodextrins (HSCDs), originally proposed by Chapman and Chen (1), is a well established and efficient approach used in many laboratories worldwide. In this study, a group of compounds was selected from a set of drugs and metabolites of pharmaceutical and forensic interest (2). This group of compounds was challenging because it included many closely related metabolites of drug substances in addition to the parentdrugs. The results confirmed those of the earlier study (1) andallowed the current strategy to be used as a model for ultra-fast methods development. The strategy has been applied in the determination of drug purity for the pharmaceutical industry. An example of purity analysis illustrates the steps and practical considerations required for a successful outcome.

Chemicals:Solutions of alpha-, beta- and gamma HSCD at a concentration of 20% w/v and all other reagents were purchased from Beckman Coulter, Fullerton, CA, USA. The reagents were prepared as per the enclosed product documentation.

Drug and Metabolite Standards:Standards were purchased from Cerilliant Corporation, Round Rock, TX, USA or were obtained as a gift from the Royal Canadian Mounted Police, Forensic Laboratory, Winnipeg, MB, Canada or Dr. Robert Meatherall, St. Boniface Hospital, Winnipeg, MB, Canada.

Solutions of these drug and metabolite standards were purchased or prepared at a concentration of 1 mg/mL and diluted to 25 ppm (25 ng/µL) in distilled and deionized water.

Reference Marker:1,3,6,8-Pyrene tetrasulfonate (PTS), 10 mM in water: 2 µL added to each sample.

Instrument:P/ACETM MDQ Capillary Electrophoresis System (Beckman Coulter, Fullerton, CA) equipped with a Photodiode Array Detector (PDAD) with detection at 200 nm (scanning 190-350) and 32 Karat™ Version 7 Software.Run Buffers: All chiral separations were performed in 5% HSCD in 25 mM triethylammonium phosphate pH 2.5 unless otherwise noted as either run in 2.5% or 7.5% of the HSCD.

Capillaries and Conditioning:Fused-silica capillaries, 50 µm I.D. x 30 cm (effective length 20 cm) were used in all separations. The columns are rinsed daily with 25 mM lithium acetate containing 0.4% Polyethylene Oxide (PEO,MW 300,000) and 10% ethylene glycol, adjusted to pH 4.75 to speed up column equilibration.

Applied Voltage:The voltage was set at 15 kV (500 V/cm) resulting in running currents of 140 to 180 µamps for 50 µm I.D. columns.

Temperatures:Capillary and sample storage = 22oC

Sample introduction:Pressure injection of 4 s at 0.3 psi or Voltage injection of 10 s at 10 kV.

Material and MethodsMaterial and Methods

ResultsResults1. Of the 692 compounds in a library used in forensic drugs screening (2), 101 were known to be racemic compounds and were used in this study.

2. At a concentration of 5% HSCD, 73 of the compounds were resolved at a resolution of 2 or higher.

3. Twenty-eight (28) of the 101 compounds were selected for additional runs at a concentration of 2.5 and 7.5% of each HSCD to further improve resolution. As a result of these runs, a total of 94% of the 101 compounds were resolved at 2 or greater.

4. Examples of the excellent resolution that can be achieved are shown in Figures 1 and 2.

Table 1: Resolution and HSCD Systems for 101 Basic Drugs and Metabolites

ConclusionConclusionFinding a universal method for chiral separations has been a challenge for many years. An important group of drugs and metabolites, expected to be frequently detected because of widespread use by the general population, was used to evaluate the proposed universal strategy. These 101 racemic drugs and metabolites are of interest to both the pharmaceutical and forensic communities. The compounds were rapidly screened and resolved with resolutions of 2 or greater for over 94% of the group.

ReferencesReferences1. Chapman, J.D and A-F. Chen, LCGC Europe, January 33 - 37 (2001)

2. Hudson, J.C. et al., Can. Soc. Forens. Sci., 31(1) 1 - 29 (1998)

Figure 3: Rapid Method Development for Purity Analysis Using Highly Sulfated Cyclodextrins

Some elements of this poster were presented at: CE in the Biotechnology & Pharmaceuticals Industries 10th Symposium on the Practical Applications for the Analysis of Proteins, Nucleotides and Small Molecules October 12-16, 2008 and at HPLC 2008, Baltimore, MD, May 10-16, 2008.

For Research Use Only; not for use in diagnostic procedures.

.

M in u te s1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0

AU

0 . 0 0 0

0 . 0 0 5

0 . 0 1 0

0 . 0 1 5

0 . 0 2 0

0 . 0 2 5

0 . 0 3 0

µA

- 1 6 0

-1 4 0

-1 2 0

-1 0 0

-8 0

-6 0

-4 0

-2 0

0

O-Desmethylvenlafaxine Venlafaxine

PTS

Figure 2: Venlafaxine and Metabolite in 5% Gamma-HSCD

Figure 1: Methoxamine in 5% Gamma-HSCD

5. This strategy was applied to a very complex racemic drug containing four chiral centers. Prior to this, the existing method used a chromatographic approach where the enantiomers were poorly resolved. To fully resolve the Active Pharmaceutical Ingredient (API) and 3 enantiomers, this systematic process was applied as follows and is illustrated in Figure 3.

Refer to steps A to E in Figure 3 (below): A. Pressure injection of the three enantiomers) at 10% of the API run in each HSCD at 5% was performed. The starting

concentation of the API was 400 nanograms per microlitre in water.B. The best resolution between 5% systems, was obtained in Beta-HSCD. Improved resolution was obtained in 7.5% Beta-HSCD. C. The capillary length was increased from 20 to 30 cm to the detector (40 cm total). D. Voltage injection from the 10% solution gave excellent sensitivity, resolution and peak shape and the sample had to be diluted 20

to 1 for the final purity determination. E. Low level purity determination result was made possible with HSCDs and voltage injection from a solution containing 400 ng/µL

of the API and 0.4 ng/µL of each enantiomer.Method development was completed in less than 3 days.

DDilution 20/1 of

the 10%Solution

Drug or Metabolite Resolution System* Drug or Metabolite Resolution System*Acebutolol 2.4 Gamma Fluoxetine, Nor- 9.8 GammaAdrenaline, Nor- (Norepinephrine) 3.5 Gamma 2.5 Glutethimide 11.8 GammaAminorex, Cis-4-methyl- 4.5 Gamma Ketamine 2.2 GammaAmphetamine 33.2 Gamma Ketamine, Nor- 4.5 AlphaAmphetamine, 2,3-Dimethoxy- 16.6 Gamma Labetolol 5.1/2.9/2.1*** Gamma 2.5Amphetamine, 2,4-Dimethoxy- 22.5 Gamma MBDB 7.5 GammaAmphetamine, 2,5-Dimethoxy- 17.2 Gamma MDA, 2,3- 16.7 GammaAmphetamine, 2,5-Dimethoxy-4-bromo- 9.9 Beta MDA, 3,4- 14.6 GammaAmphetamine, 2,5-Dimethoxy-4-ethyl- 11.6 Gamma MDEA, 3,4- 7.1 GammaAmphetamine, 2,5-Dimethoxy-4-methyl- 13.8 Gamma MDMA, 2,3- 9.7 GammaAmphetamine, 2,5-Dimethoxy-4-propyl- 6.0 Gamma MDMA, 3,4- 7.8 GammaAmphetamine, 2,6-Dimethoxy- 4.5 Gamma Methadone 26.6 BetaAmphetamine, 3,4-Dimethoxy- 14.4 Gamma Methamphetamine 11.8 GammaAmphetamine, 3,5-Dimethoxy- 4.6 Gamma Methoxamine 44.4 GammaAmphetamine, 3-Methoxy-4,5-methylenedioxy- 4.6 Gamma Methylphenidate 14.5 GammaAmphetamine, N-Ethyl- 14.7 Gamma Metoprolol 4.2 Alpha 2.5Amphetamine, 4-Methylthio- (4-MTA) 13.4 Gamma Mexilitine 2.7 Gamma 7.5Amphetamine, Hydroxy- 30.6 Gamma Midazolam 3.1 GammaAtenolol 3.4 Gamma Mirtazapine 5.4 GammaBisoprolol 2.2 Gamma 2.5 Mirtazepine, N-Desmethyl 7.5 GammaBrompheniramine, Dinor- 0.8 Beta 7.5 Nadolol 2.6/1.3/split*** GammaBrompheniramine, Nor- 1.0 Beta Nefopam 7.6 AlphaBupropion 10.1 Alpha Oxprenolol 10.0 BetaBupropion, Erythroamino- 7.5 Gamma Pentazocine 7.2 Gamma 7.5Bupropion, Hydroxy- 6.3 Beta Pheniramine 2.8 Beta 7.5Bupropion, Threoamino- 7.6 Alpha Phenmetrazine 19.5 AlphaButriptyline, N-desmethyl- 1.1 Alpha Phenylephrine, N-Desmethyl- 3.6 AlphaChloroquine, N,N,-Didesethyl- 1.9 Gamma 7.5 Phenylpropanolamine 42.6 GammaChloroquine, N-Desethyl- 1.1 Alpha Pindolol 2.0 Beta 7.5Chlorpheniramine 2.5 Beta 7.5 PMA (p-Methoxyamphetamine) 25.3 GammaChlorpheniramine, Dinor- 1.0 Beta 7.5 PMMA (p-Methoxymethamphetamine) 13.1 GammaChlorpheniramine, Nor- 1.1 Beta 7.5 Propranolol 4.3 Alpha 2.5Citalopram 11.1 Gamma Pronethalol 2.5 Alpha 2.5Citalopram N-Oxide 11.0 Gamma Propoxyphene 7.3 AlphaCitalopram, Dinor- 8.0 Gamma Pseudoephedrine 5.2 GammaCitalopram, Nor- 8.0 Gamma Quetiapine 4.4 GammaCyclazocine 3.8 Beta Quinidine 2.3 AlphaCyclobenzaprine 1.9 Gamma 7.5 Salbutamol 8.3 BetaCyclobenzaprine, N-Desmethyl- 5.4 Alpha Tetramisole 3.6 GammaDesloratadine 6.4 Gamma Tramadol 13.3 GammaDihydro-N,N-dimethyl-5-methylene- ** 3.2 Alpha Tramadol, Nor- 10.3 GammaDisopyramide, p-Cl 4.7 Beta Trimipramine 7.3 AlphaDisopyramide, N-Dealkylated- 4.6 Alpha Trimipramine, Nor- 2.0 AlphaDoxapram 7.2 Gamma Venlafaxine 5.5 GammaDoxylamine 2.2 Gamma 7.5 Venlafaxine, O-Desmethyl- 4.3 GammaEDDP (Methadone Mtb.) 3.0 Beta 7.5 Verapamil 7.1 AlphaEMDP (Methadone Mtb.) 7.5 Gamma Verapamil, Nor- 6.9 AlphaEphedrine 6.1 Alpha Zopiclone 24.0 GammaEphedrine, Hydroxy 15.6 Gamma Zopiclone N-Oxide 23.6 GammaEsmolol 3.1 Gamma Zopiclone, Nor- 31.6 GammaFluoxetine 12.0 Alpha 2.5

* All systems 5% HSCD unless indicated otherwise ** Dihydro-N,N-dimethyl-5-methylene-5H-dibenzocycloheptene-10-ethanamine, 10,11-*** Compound with 2 chiral centers

BC

PDA Detection of Enantiomers & API

E

A

Dilution 20/1 of

the 10% Solution

Rapid Enantiomeric Separation of Basic Drugs and Metabolites:

A Universal Strategy for Ultra-Fast Method Development.

John C. Hudson and Hans A. Dewald,

Beckman Coulter, Inc., Fullerton, CA, USA

Introduction

This work describes the use of charged cyclodextrins in a continuing search for a universal strategy for separation of enantiomeric drug substances. The use of highly sulfated cyclodextrins (HSCDs), originally proposed by Chapman and Chen (1), is a well established and efficient approach used in many laboratories worldwide. In this study, a group of compounds was selected from a set of drugs and metabolites of pharmaceutical and forensic interest (2). This group of compounds was challenging because it included many closely related metabolites of drug substances in addition to the parent drugs. The results confirmed those of the earlier study (1) and allowed the current strategy to be used as a model for ultra-fast methods development. The strategy has been applied in the determination of drug purity for the pharmaceutical industry. An example of purity analysis illustrates the steps and practical considerations required for a successful outcome.

Chemicals:

Solutions of alpha-, beta- and gamma HSCD at a concentration of 20% w/v and all other reagents were purchased from Beckman Coulter, Fullerton, CA, USA. The reagents were prepared as per the enclosed product documentation.

Drug and Metabolite Standards:

Standards were purchased from Cerilliant Corporation, Round Rock, TX, USA or were obtained as a gift from the Royal Canadian Mounted Police, Forensic Laboratory, Winnipeg, MB, Canada or Dr. Robert Meatherall, St. Boniface Hospital, Winnipeg, MB, Canada.

Solutions of these drug and metabolite standards were purchased or prepared at a concentration of 1 mg/mL and diluted to 25 ppm (25 ng/µL) in distilled and deionized water.

Reference Marker:

1,3,6,8-Pyrene tetrasulfonate (PTS), 10 mM in water:

2 µL added to each sample.

Instrument:

P/ACETM MDQ Capillary Electrophoresis System (Beckman Coulter, Fullerton, CA) equipped with a Photodiode Array Detector (PDAD) with detection at 200 nm (scanning 190-350) and 32 Karat™ Version 7 Software.

Run Buffers: All chiral separations were performed in 5% HSCD in 25 mM triethylammonium phosphate pH 2.5 unless otherwise noted as either run in 2.5% or 7.5% of the HSCD.

Capillaries and Conditioning:

Fused-silica capillaries, 50 µm I.D. x 30 cm (effective length 20 cm) were used in all separations. The columns are rinsed daily with 25 mM lithium acetate containing 0.4% Polyethylene Oxide (PEO,MW 300,000) and 10% ethylene glycol, adjusted to pH 4.75 to speed up column equilibration.

Applied Voltage:

The voltage was set at 15 kV (500 V/cm) resulting in running currents of 140 to 180 µamps for 50 µm I.D. columns.

Temperatures:

Capillary and sample storage = 22oC

Sample introduction:

Pressure injection of 4 s at 0.3 psi or

Voltage injection of 10 s at 10 kV.

Material and Methods

Results

1. Of the 692 compounds in a library used in forensic drugs screening (2), 101 were known to be racemic compounds and were used in this study.

2. At a concentration of 5% HSCD, 73 of the compounds were resolved at a resolution of 2 or higher.

3. Twenty-eight (28) of the 101 compounds were selected for additional runs at a concentration of 2.5 and 7.5% of each HSCD to further improve resolution. As a result of these runs, a total of 94% of the 101 compounds were resolved at 2 or greater.

4. Examples of the excellent resolution that can be achieved are shown in Figures 1 and 2.

Table 1: Resolution and HSCD Systems for 101 Basic Drugs and Metabolites

Conclusion

Finding a universal method for chiral separations has been a challenge for many years. An important group of drugs and metabolites, expected to be frequently detected because of widespread use by the general population, was used to evaluate the proposed universal strategy. These 101 racemic drugs and metabolites are of interest to both the pharmaceutical and forensic communities. The compounds were rapidly screened and resolved with resolutions of 2 or greater for over 94% of the group.

References

1. Chapman, J.D and A-F. Chen, LCGC Europe, January 33 - 37 (2001)

2. Hudson, J.C. et al., Can. Soc. Forens. Sci., 31(1) 1 - 29 (1998)

Figure 3: Rapid Method Development for Purity Analysis Using Highly Sulfated Cyclodextrins

Some elements of this poster were presented at: CE in the Biotechnology & Pharmaceuticals Industries 10th Symposium on the Practical Applications for the Analysis of Proteins, Nucleotides and Small Molecules October 12-16, 2008 and at HPLC 2008, Baltimore, MD, May 10-16, 2008.

For Research Use Only; not for use in diagnostic procedures.

.

O-Desmethylvenlafaxine

Venlafaxine

PTS

Figure 2: Venlafaxine and Metabolite in 5% Gamma-HSCD

Figure 1: Methoxamine in 5% Gamma-HSCD

5. This strategy was applied to a very complex racemic drug containing four chiral centers. Prior to this, the existing method used a chromatographic approach where the enantiomers were poorly resolved. To fully resolve the Active Pharmaceutical Ingredient (API) and 3 enantiomers, this systematic process was applied as follows and is illustrated in Figure 3.

Refer to steps A to E in Figure 3 (below):

A. Pressure injection of the three enantiomers) at 10% of the API run in each HSCD at 5% was performed. The starting concentation of the API was 400 nanograms per microlitre in water.

B. The best resolution between 5% systems, was obtained in Beta-HSCD. Improved resolution was obtained in 7.5% Beta-HSCD.

C. The capillary length was increased from 20 to 30 cm to the detector (40 cm total).

D. Voltage injection from the 10% solution gave excellent sensitivity, resolution and peak shape and the sample had to be diluted 20 to 1 for the final purity determination.

E. Low level purity determination result was made possible with HSCDs and voltage injection from a solution containing 400 ng/µL of the API and 0.4 ng/µL of each enantiomer.

Method development was completed in less than 3 days.

D

B

C

PDA Detection of Enantiomers & API

E

A

Drug or Metabolite Resolution System* Drug or Metabolite Resolution System*

Acebutolol 2.4Gamma Fluoxetine, Nor- 9.8Gamma

Adrenaline, Nor- (Norepinephrine) 3.5Gamma 2.5 Glutethimide 11.8Gamma

Aminorex, Cis-4-methyl- 4.5Gamma Ketamine 2.2Gamma

Amphetamine 33.2Gamma Ketamine, Nor- 4.5Alpha

Amphetamine, 2,3-Dimethoxy- 16.6Gamma Labetolol 5.1/2.9/2.1*** Gamma 2.5

Amphetamine, 2,4-Dimethoxy- 22.5Gamma MBDB 7.5Gamma

Amphetamine, 2,5-Dimethoxy- 17.2Gamma MDA, 2,3- 16.7Gamma

Amphetamine, 2,5-Dimethoxy-4-bromo- 9.9Beta MDA, 3,4- 14.6Gamma

Amphetamine, 2,5-Dimethoxy-4-ethyl- 11.6Gamma MDEA, 3,4- 7.1Gamma

Amphetamine, 2,5-Dimethoxy-4-methyl- 13.8Gamma MDMA, 2,3- 9.7Gamma

Amphetamine, 2,5-Dimethoxy-4-propyl- 6.0Gamma MDMA, 3,4- 7.8Gamma

Amphetamine, 2,6-Dimethoxy- 4.5Gamma Methadone 26.6Beta

Amphetamine, 3,4-Dimethoxy- 14.4Gamma Methamphetamine 11.8Gamma

Amphetamine, 3,5-Dimethoxy- 4.6Gamma Methoxamine 44.4Gamma

Amphetamine, 3-Methoxy-4,5-methylenedioxy- 4.6Gamma Methylphenidate 14.5Gamma

Amphetamine, N-Ethyl- 14.7Gamma Metoprolol 4.2Alpha 2.5

Amphetamine, 4-Methylthio- (4-MTA) 13.4Gamma Mexilitine 2.7Gamma 7.5

Amphetamine, Hydroxy- 30.6Gamma Midazolam 3.1Gamma

Atenolol 3.4Gamma Mirtazapine 5.4Gamma

Bisoprolol 2.2Gamma 2.5 Mirtazepine, N-Desmethyl 7.5Gamma

Brompheniramine, Dinor- 0.8Beta 7.5 Nadolol 2.6/1.3/split*** Gamma

Brompheniramine, Nor- 1.0Beta Nefopam 7.6Alpha

Bupropion 10.1Alpha Oxprenolol 10.0Beta

Bupropion, Erythroamino- 7.5Gamma Pentazocine 7.2Gamma 7.5

Bupropion, Hydroxy- 6.3Beta Pheniramine 2.8Beta 7.5

Bupropion, Threoamino- 7.6Alpha Phenmetrazine 19.5Alpha

Butriptyline, N-desmethyl- 1.1Alpha Phenylephrine, N-Desmethyl- 3.6Alpha

Chloroquine, N,N,-Didesethyl- 1.9Gamma 7.5 Phenylpropanolamine 42.6Gamma

Chloroquine, N-Desethyl- 1.1Alpha Pindolol 2.0Beta 7.5

Chlorpheniramine 2.5Beta 7.5 PMA (p-Methoxyamphetamine) 25.3Gamma

Chlorpheniramine, Dinor- 1.0Beta 7.5 PMMA (p-Methoxymethamphetamine) 13.1Gamma

Chlorpheniramine, Nor- 1.1Beta 7.5 Propranolol 4.3Alpha 2.5

Citalopram 11.1Gamma Pronethalol 2.5Alpha 2.5

Citalopram N-Oxide 11.0Gamma Propoxyphene 7.3Alpha

Citalopram, Dinor- 8.0Gamma Pseudoephedrine 5.2Gamma

Citalopram, Nor- 8.0Gamma Quetiapine 4.4Gamma

Cyclazocine 3.8Beta Quinidine 2.3Alpha

Cyclobenzaprine 1.9Gamma 7.5 Salbutamol 8.3Beta

Cyclobenzaprine, N-Desmethyl- 5.4Alpha Tetramisole 3.6Gamma

Desloratadine 6.4Gamma Tramadol 13.3Gamma

Dihydro-N,N-dimethyl-5-methylene- ** 3.2Alpha Tramadol, Nor- 10.3Gamma

Disopyramide, p-Cl 4.7Beta Trimipramine 7.3Alpha

Disopyramide, N-Dealkylated- 4.6Alpha Trimipramine, Nor- 2.0Alpha

Doxapram 7.2Gamma Venlafaxine 5.5Gamma

Doxylamine 2.2Gamma 7.5 Venlafaxine, O-Desmethyl- 4.3Gamma

EDDP (Methadone Mtb.) 3.0Beta 7.5 Verapamil 7.1Alpha

EMDP (Methadone Mtb.) 7.5Gamma Verapamil, Nor- 6.9Alpha

Ephedrine 6.1Alpha Zopiclone 24.0Gamma

Ephedrine, Hydroxy 15.6Gamma Zopiclone N-Oxide 23.6Gamma

Esmolol 3.1Gamma Zopiclone, Nor- 31.6Gamma

Fluoxetine 12.0Alpha 2.5

* All systems 5% HSCD unless indicated otherwise ** Dihydro-N,N-dimethyl-5-methylene-5H-dibenzocycloheptene-10-ethanamine, 10,11-

*** Compound with 2 chiral centers

Minutes

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

8.0

AU

0.000

0.005

0.010

0.015

0.020

0.025

0.030

µA

-160

-140

-120

-100

-80

-60

-40

-20

0

administrator�MSB 2009 Poster Hudson V144x34.ppt�

/ColorImageDict > /JPEG2000ColorACSImageDict > /JPEG2000ColorImageDict > /AntiAliasGrayImages false /DownsampleGrayImages false /GrayImageDownsampleType /Bicubic /GrayImageResolution 150 /GrayImageDepth -1 /GrayImageDownsampleThreshold 1.50000 /EncodeGrayImages true /GrayImageFilter /DCTEncode /AutoFilterGrayImages true /GrayImageAutoFilterStrategy /JPEG /GrayACSImageDict > /GrayImageDict > /JPEG2000GrayACSImageDict > /JPEG2000GrayImageDict > /AntiAliasMonoImages false /DownsampleMonoImages false /MonoImageDownsampleType /Bicubic /MonoImageResolution 300 /MonoImageDepth -1 /MonoImageDownsampleThreshold 1.50000 /EncodeMonoImages true /MonoImageFilter /CCITTFaxEncode /MonoImageDict > /AllowPSXObjects true /PDFX1aCheck false /PDFX3Check false /PDFXCompliantPDFOnly false /PDFXNoTrimBoxError true /PDFXTrimBoxToMediaBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXSetBleedBoxToMediaBox true /PDFXBleedBoxToTrimBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXOutputIntentProfile () /PDFXOutputCondition () /PDFXRegistryName (http://www.color.org) /PDFXTrapped /False

/Description >>> setdistillerparams> setpagedevice