Mantu K. Ghosh

HPLC Methods on Drug Analysis

Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Hong Kong Barcelona Budapest

Dr. Mantu Kumar Ghosh 4420 Coesfeld, Germany

Library of Congress Cataloging in Publication Data Ghosh, Mantu K. (Mantu Kumar), 1942-HPLC methods on drug analysis / Mantu K. Ghosh. Includes index.

ISBN-13: 978-3-540-53824-0 DOl: 10.1007/978-3-642-76506-3

e-ISBN-13: 978-3-642-76506-3

I. High performance liquid chromatography - Laboratory manuals. 2. Drugs - Analysis - Laboratory manuals. I. Title. [DNLM: I. Chromatography, High Pressure Liquid - methods - laboratory manuals. 2. Drugs - analysis laboratory manuals. QV 25 G427h] RSI89.5.H54G47 1992 615'. 1901--dc20 DNLM/DLC

This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, re-use of illustra­tions, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication of this publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, 1965, in its current version and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. Neither the author nor the publisher is responsible for the reproducibility of the described methods.

© Springer-Verlag Berlin Heidelberg 1992

The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and thereof free for general use.

Typesetting: Macmillan India Ltd. Bangalore 25. 52/3020-54321O-Printed on acid-free paper.

Dedicated to the memory of my parents

Contents

1 Preface............. IX

2 Abbreviations......... XI

3 List of the Described Drugs xiii 4 Explanatory Notes. . . . . . 1 5 Drug Monographs. . . . . . 5 6 Conversion of Imperial and SI Unit Equivalents of other Units 570 7 Atomic Mass of the Elements . 573 8 Miscibility of Solvents. . . . . . . . . . . . . . . . . . . . . . . 576 9 Characteristics of the Solvents. . . . . . . . . . . . . . . . . . 578 10 Characteristics of the Common HPLC Separation Systems

(columns) . . . . . . . . . . 580 11 Sorbent Selection Guides. . . . . . . . . . . . . . . . . . . . . 584

Preface

The dramatic development of chromatographic techniques, specially high per­formance or high pressure liquid chromatography (HPLC) has made possible the easy analysis of organic compounds, including drugs and drug components, for last two decades.

This rapid increase and improvement of analytical methodology with HPLC has enabled researchers and scientists to cope with other scientific and instru­mental developments in their fields of work.

Thousands of impressive and original scientific publications, text books and monographs describe the techniques for drug analysis with high performance liquid chromatography. However, no concise presentation of the general proper­ties of the drugs and their HPLC methodology exists together in the market. This work contains the general properties necessary for the analysis of 232 drugs as well as the HPLC methods for many other drugs and drug components. It is hoped that it will fill a gap and provide a precise survey of the HPLC methods for drug analysis. It is intended as an immediate guide in the laboratory and will be of help to the scientists, researchers and technicians in the field of analysis.

This book describes approx. 1300 HPLC methods, in a precise form, for the analysis of some hundreds of drugs and drug components from raw materials, pharmaceuticals and biological samples under 232 headings. Emphasis is laid on the important points of the general properties of the described drugs, extraction, apparatus, column, eluent, temperature, injection size, detection, retention times and references whereever possible. The tabular presentation is very easy to understand with minimum knowledge of chemistry as well as of HPLC for the quantitative analysis of drugs.The preservatives used in drugs are considered, since they are also a part of the pharmaceutical formulations in most cases, and some autocoids used for diagnostic purposes or treatment are also described here.

I must express my love for and gratitude to my wife, Manikuntala Ghosh, B.Sc. for her direct help in the preparation of the manuscript. I highly appreciate and thank Mrs. K. Rausse, Muenster, for her patience in typing the manuscript. I also take this opportunity to thank many of my friends for their inspiration for this work to become a reality.

Coesfeld, Germany, M.K. Ghosh

Abbreviations

A ampere ID inner diameter Afs ampere full scale In inch r1 alpha insol insoluble appr. approximately IV international unit aq aqueous k' (column) capacity factor or AU absorbance units capacity ratio AUFS absorbance units full scale kg kilogram ~ beta kPa kilopascal BP British Pharmacopoeia I liter °C degree Celsius, centigrade Ib,lbs pound, pounds CAS chemical abstract service LC liquid chromatography Ci curie LDC Laboratory Data Control cm centimeter L levo (rotatory) CNS central nervous system m milli ( = 10 - 3); also, meter D dextro (rotatory) m meta-S delta M molar (mol/I) or model EC electrochemical (apparatus) Ed editor or edited by max maximum Edn edition mg milligram EDTA ethylenediaminetetraacetic acid min minute em emission ml milliliter et al. et alii, 'and others' for more mm millimeter

than three co-authors mM millimole eV electron volt mol mole ex excitation MPa mega pascal OF degree Fahrenheit mV millivolt FID flame ionization detector ~ micro ( = 10 - 6); also, ionic fg femtogram ( = 10 - 1 5 g) strength fmol femtomol ~g microgram ( = 10- 6 g) FS full scale ~I microliter ( = 10- 6 1) fsd full scale deflection ~m micrometer g gram (10- 6 m = 10- 4 cm) y gamma n nano ( = 10- 9 );

GC glassy carbon (electrode) normal in organic names, e.g., h hour n-butylamine HP Hewlett-Packard N normal (solution); nitrogen, e.g., HPLC high-performance liquid N-Acety1cysteine

chromatography; also, NF National Formulary high-pressure liquid ng nanogram ( = 10 - 9 g) chromatography nm nanometer ( = 10- 9 m)

i (or ~) ionic strength nM nanomol

xii Abbreviations

No number RI refractive index NP normal phase RP reversed-phase 0- ortho- RT retention times 0 attachment to oxygen S stereo (isomer) p- para- s second Pa pascal sol solution or soluble pg picogram ( = 10 - 12 g) SP Spectra-Physics pH hydrogen ion exponent "- lambda (wavelength, nm) PLRP polymeric reversed-phase tert.- tertiary, e.g., tert.-butanol pmol picomol USP United States Pharmacopeia ppb parts per billion UV ultraviolet ppm parts per million V volt PRP polymeric reversed-phase VIS visible psi pounds per square inch vs versus, against R racemic (isomer) v/v volume per volume RCM radial compression module w/v weight per volume RCSS radial compression separation w/w weight per weight

system > greater than; faster than RE reference electrode < less than; slower than ref. reference degree(s) Celsius, centigrade

List of the Described Drugs

1 Acetylcysteine, 5 2 Acetylsalicylic Acid, 6 3 Acyclovir, 9 4 Allopurinol, 10 5 Amiodarone, 13 6 Amitriptyline, 15 7 Amobarbital, 19 8 Amoxicillin, 22 9 Amphetamine, 25 10 Amphotericin B, 27 11 Ampicillin, 30 12 Ascorbic Acid, 32 13 Atropine, 35

14 Bacampicillin, 37 15 Bacitracin, 39 16 Beclomethasone, 42 17 Benzalkonium Chloride, 43 18 Benzyl Alcohol, 44 19 Benzylpenicillin, 46 20 Betamethasone, 49 21 Bleomycin Sulfate, 51 22 Bupivacaine Hydrochloride, 54

23 Caffeine, 56 24 Carbamazepine, 58 25 Carbenicillin, 61 26 Cefamandole, 64 27 Cefazolin Sodium, 66 28 Cefixime, 68 29 Cefotaxime, 69 30 Ceftriaxone, 72 31 Cephalexin, 73 32 Cephalothin, 77 33 Cephradine, 79 34 Chlorambucil, 81 35 Chloramphenicol, 83 36 Clordiazepoxide, 86 37 Chloroquinine, 88

38 Chlorothiazide, 91 39 Chlorpheniramine, 93 40 Chlorpromazine, 96 41 Chlorpropamide, 100 42 Chlorprothixene, 101 43 Chlortetracycline, 105 44 Chlorthalidone, 108 45 Choline, 110 46 Cimetidine, 112 47 Clavulanic Acid, 115 48 Clindamycin, 117 49 Clonalepam, 119 50 Clonidine, 122 51 Cloxacillin, 123 52 Cocaine, 126 53 Codeine, 129 54 Colistin, 131 55 Cortisone, 133 56 Cyanocobalamin, 136 57 Cyclosporin A, 139

58 Daunorubicin, 142 59 Deoxycortone, 145 60 Dexamethasone, 147 61 Dextrose, 150 62 Diazepam, 152 63 Dicloxacillin, 155 64 Dicoumarol, 157 65 Digitoxin, 158 66 Digoxin, 161 67 Diltiazem Hydrochloride, 164 68 Dimetridazole, 167 69 Dopa (Levodopa), 169 70 Dopamine, 171 71 Doxorubicin (Adriamycin), 174 72 Doxycycline, 178

73 Ephedrine, 180 74 Epinephrine, 184

XIV List of the Described Drugs

75 Ergometrine, 188 76 Ergotamine, 190 77 Erythromycin, 192 78 Estradiol, 195

79 Fenbendazole, 199 80 Fentanyl, 201 81 Flumequine, 202 82 5-FluorouraciI, 203 83 Flurbiprofen, 206 84 Folic Acid, 207 85 Fructose, 209 86 Furazolidone, 211 87 Furosemide, 213

88 Gentamicin, 216 89 Globulins, 219 90 Griseofulvin, 221

91 Haloperidol, 223 92 Heroin, 226 93 Hexobarbital, 229 94 Histamine, 231 95 Hydrocortisone, 232

96 Ibuprofen, 236 97 Idoxuridine, 239 98 Imipramine, 240 99 Indomethacin, 243 100 Insulin, 245 10 1 Isoniazid, 248 102 Isoprenaline, 251 103 I vermectin, 252

104 Kanamycin, 255 105 Ketamine, 258 106 Ketoconazole, 259 107 Ketoprofen, 261

108 Labetalol, 265 109 Lactose, 267 110 Levamisole, 270 111 Lidocaine, 271 112 Lorazepam, 274 113 Lysergide (LSD), 277

114 Mebendazole, 279 115 Meclizine, 281 116 Medazepam, 282 117 Medroxyprogesterone Acetate, 284 118 Melphalan, 286 119 Mepyramine, 289 120 Methadone, 290 121 Methylparaben, 293 122 Metronidazole, 295 123 Mezlocillin, 297 124 Miconazole, 299 125 Minoxidil, 301 126 Morphine, 302

127 NadoloI, 305 128 Nalidixic Acid, 308 129 Naloxone, 310 130 Nandrolone, 312 131 Neomycin, 314 132 Nicotinamide, 317 133 Nicotine, 319 134 Nifedipine, 321 135 Nitrofurantoin, 324 136 Nitrofurazone, 325 137 Nitroglycerin, 327 138 Norepinephrine, 330 139 Novobiocin, 332 140 Nystatin, 335

141 Oleandomycin, 336 142 Oxazepam, 338 143 Oxytetracycline Dihydrate, 341 144 Oxytocin, 345

145 Pantothenic Acid, 347 146 Paracetamol, 349 147 Penicillin V, 354 148 Pentobarbital, 356 149 Phenacetin, 358 150 Phenazone, 361 151 Pheniramine, 363 152 Phenobarbital, 365 153 Phenol, 368 154 Phenprocoumon, 370 155 Phenylbutazone, 372 156 Phenytoin, 374 157 Physostigmine, 377 158 Pilocarpine, 379

159 Piperaci1lin, 382 160 Polymyxin B Sulfate, 384 161 Poly thiazide, 387 162 Prednisolone, 389 163 Prednisone, 391 164 Procainamide, 394 165 Procaine, 397 166 Progesterone, 399 167 Promazine, 403 168 Promethazine, 405 169 Propranolol, 408 170 Propylparaben, 411 171 Prostaglandine F2., 413 172 Pseudoephedrine, 416 173 Pyrantel, 419 174 Pyridostigmine Bromide, 420 175 Pyridoxine, 422 176 Pyrimethamine, 425

177 Quinidine, 427 178 Quinine, 430

179 Ranitidine, 433 180 Reserpine, 436 181 Ribavirin, 437 182 Riboflavine, 439 183 Rifampicin, 441

184 Salicylamide, 445 185 Salicylic Acid, 448 186 Secobarbital, 451 187 Serotonin, 453 188 Spectinomycin, 456 189 Spironolactone, 457 190 Stilbestrol, 460 191 Streptomycin and

Dihydrostreptomycin, 463 192 Strychnine, 465 193 Sucrose, 468 194 Sulfadiazine, 471 195 Sulfaguanidine, 473 196 Sulfamerazine, 475 197 Sulfamethazine, 478

List of the Described Drugs xv

198 Sulfamethoxazole, 481 199 Sulfanilamide, 483 200 Sulfapyridine, 486 201 Sulfathiazole, 489

202 Temazepam, 492 203 Terbutaline, 494 204 Testosterone, 496 205 Tetracycline, 500 206 Tetroxoprim, 504 207 Thalidomide, 505 208 Theobromine, 507 209 Theophylline, 511 210 Thiabendazole, 514 211 Thiamine, 516 212 Thiamphenicol, 519 213 Thiopental, 520 214 Ticarcillin, 523 215 Tobramycin, 525 216 Tocainide, 526 217 Tolbutamide, 529 218 Triamcinolone, 532 219 Triclabendazole, 534 220 Trimethoprim, 535 221 Tripelennamine, 538 222 Tubocurarine Chloride, 540 223 Tylosin, 541

224 Vancomycin, 544 225 Verapamil, 547 226 Vitamin A, 550 227 Vitamin 0 3, 554 228 Vitamin E, 556 229 Vitamin K" 559

230 Warfarin, 562

231 Xylazine, 565

232 Yohimbine, 567