In this specific context the remarkable proliferation of windows-based computer software stretched overwhelmingly towards instrument control, real time data handling abilities and the ultimate usage of Laboratory Information Management Systems (LIMS) are surprisingly noteworthy. "Pharmaceutical Drug Analysis" in its present form essentially comprise of six parts containing in all thirty-two well-elaborated chapters predominantly dealing with the set of descriptive analytical methodologies developed to control and assure the quality of the final marketed product; and, therefore, includes both qualitative and quantitative methods of analysis to help in the identification as well as purity of the product. The main purpose of this textbook is to discuss in an explicit and lucid manner several of the newer methods that now find rather wider application in the domain of pharmaceutical analysis. The basic principle of each technique is critically treated with emphasis on factors that directly affect its proper and judicious application to various analytical problems. An in-depth knowledge of these principles, instrumentations, modus operandi, experimental parameters, and sample preparation procedures in order to optimize the performance procedure of typical assay of pharmaceutical secondary products i.e., dosage forms, calculations etc., along with cognate assays from the Official Compendia have been included profusely. Undergraduate and postgraduate students of pharmaceutical drug analysis, quality assurance chemists, industrial trainees, bulk-drug professionals and those in related disciplines earnestly requiring a substantial fundamental understanding and knowledge of the subject will certainly find this a much needed suitable compilation for reading and reference. The broad coverage included in each of the selected analytical techniques would render "Pharmaceutical Drug Analysis" to be an useful source of ideas, inspiration for research, and developing newer practical solutions to problems in the ever expanding field of pharmaceutical analysis.
Author(s): Ashutosh Kar
Edition: 2nd edition
Publisher: New Age International Pvt Ltd Publishers
Year: 2005
Language: English
Pages: 554
Preface to the Second Edition......Page 8
Preface to the First Edition......Page 10
Contents......Page 14
Part l General Aspects......Page 26
1.1 Introduction......Page 28
1.2.1 Broad-Based Highest Attainable Standard......Page 29
1.2.3 Official Standards vis-a-vis Manufacturing Standards
......Page 30
1.3.2 Sampling Procedures and Errors......Page 31
1.3.3 Bioavailability......Page 34
1.3.4 Identification Tests......Page 35
1.3.5 Physical Constants......Page 36
1.3.7 Various Types of Tests for Quantitative Determinations......Page 42
1.3.8 Limit Tests for Metallic Impurities......Page 50
1.3.9 Limit Test's for Acid Radical Impurities......Page 55
1.3.10 Limit Tests for Non-Metallic Impurities......Page 62
2.1 Introduction......Page 66
2.2.2 Definitions......Page 67
2.2.3 Volumetric Apparatus......Page 69
2.2.4 General Considerations......Page 76
2.2.5 Technique of Volumetric Analysis......Page 77
2.4.1 Colorimetric Assays......Page 78
2.4.2 Enzymatic Assays......Page 83
2.4.3 Radioimmuno Assays (RIAS)......Page 88
2.4.4 Automated Methods of Clinical Analysis......Page 91
3A.1. Introduction......Page 96
3A.2.1. Determinate (Systematic) Errors......Page 97
3A.2.2. Indeterminate (Random) Errors......Page 98
3A.2.4. Precision......Page 99
3A.2.5 Minimising Systematic Errors......Page 100
3B.2.1 Statistical Treatement of Finite Samples......Page 102
3B.2.2. Distribution of Random Numbers......Page 104
3B.2.3 Significant Figures......Page 105
3B.2.4 Comparison of Results......Page 106
3B.2.5 Method of Least Squares......Page 108
3B.2.6 Recommendations for Criteria of Rejecting an Observation......Page 110
3B.2.7 Sampling Statistics......Page 112
Part ll Chemical Methods......Page 116
A. Titrimetric Methods: Acidimetry and Alkalimetry......Page 118
4.1.1 Lowry and Bronsted's Theory of Acid and Bases......Page 120
4.1.3 Usanovich Theory......Page 122
4.3 Assay of Drugs
......Page 123
4.3.1 Direct Titration Method......Page 124
4.3.2 Residual Titration Method......Page 125
4.4 Theory of Alkalimetry......Page 126
4.4.1 Direct Titration Method (DTM)......Page 127
4.4.2 Residual Titration Methods (RTM)......Page 128
5.1 Introduction......Page 131
5.2.1 Solvents......Page 132
5.3.1 Preparation of 0.1 N Perchloric Acid......Page 133
5.3.2 Standardization of 0.1 N Perchloric Acid......Page 134
5.4 Assay by Non-Aqueous Titrations......Page 135
5.4.1 Acidimetry in Non-Aqueous Titrations
......Page 136
5.4.2 Alkalimetry in Non-Aqueous Titrations......Page 142
B. Redox Methods......Page 148
6.2 Theory......Page 150
6.3.1 Permanganate Methods......Page 151
6.3.2 Dichromate Methods......Page 155
6.3.3 Ceric Sulphate Titration Methods......Page 158
7.2 Theory......Page 162
7.3.1 Iodimetric Assays......Page 163
7.3.2 Iodometric Assays......Page 169
C. Precipitation Methods......Page 174
8.1 Introduction......Page 176
8.3 Assay Methods......Page 177
8.3.1 Direct Titration with Silver Nitrate
......Page 178
8.3.2 Ammonium Thiocyanate-Silver Nitrate Titrations (Volhard's Method)
......Page 180
D.Complexometric Methods......Page 184
9.2 Theory......Page 186
9.2.2 Stability of Complexes......Page 188
9.2.5 Usage of pM Indicators in Complexometric Titrations
......Page 189
9.3 Assay Methods......Page 190
9.3.1 Direct Titration Methods
......Page 191
9.3.2 Masking and Demasking Agents......Page 193
9.3.3 Residual Titration Methods......Page 194
E. Gravimetric Methods......Page 196
10.2 Theory......Page 198
10.2.1 Law of Mass Action and Reversible Reactions......Page 199
10.2.2 Principle of Solubility of Product......Page 200
10.2.3 Comnion Ion Effect......Page 201
10.3.1 Substances Assayed Gravimetrically......Page 202
10.3.2 Substances Assayed After Conversion......Page 206
F. Thermoanalytical Methods......Page 216
11.1 Introduction......Page 218
11.2.2 Instrumentation......Page 219
11.2.3 Methodology......Page 220
11.3.2 Instrumentation......Page 223
11.3.3 Methodology......Page 224
11.4.2 Instrumentation......Page 225
11.4.4 Applications......Page 227
G. Miscellaneous Methods......Page 230
12.2 Theory......Page 232
12.3.2 Standardization of 0.1 M Sodium Nitrite Solution with Sulphanilamide......Page 233
12.3.4 Isocarboxazid......Page 234
12.3.6 Cognate Assays......Page 235
13.1 Introduction......Page 238
13.3.1 Titrations with 0.1 N Bromine......Page 239
13.3.2 Titrations with Potassium Bromate......Page 242
13.3.3 Titrations with Potassium Iodate......Page 244
14.2 Theory......Page 248
14.3 Instrumentation......Page 249
14.3.1 Automated Electrochemical Karl Fischer Analysis......Page 250
14.4.2 Cognate Assays......Page 251
15.2 Theory......Page 253
15.3.1 Hydrocortisone Acetate......Page 254
15.3.2 Cognate Assays......Page 255
Part lll Electrochemical Methods......Page 256
16.2 Theory......Page 258
16.2.1 General Considerations......Page 260
16.2.2 End-Point Determination......Page 262
16.3. Instrumentation......Page 264
16.3.1 Electrodes......Page 265
16.3.2 Automatic Titrator (Preset End-Point Titrator)......Page 274
16.4 Applications of Potentiometric Titrations in Pharmaceutical Analysis......Page 275
16.4.1 Cognate Assays......Page 276
17.1 Introduction......Page 278
17.2.1 Titration Curves......Page 279
17.2.2 Corrections for the Volume Change......Page 281
17.3.1 Amperometric Titrations with the Dropping Mercury Electrode......Page 282
17.3.2 Amperometric Titrations with a Rotating Platinum Microelectrode......Page 283
17.3.3 Amperometric Titrations with Twin-Polarized Microelectrodes(Biamperometric Titrations or Dead-Stop-End-Point Method)......Page 285
17.4.4 Assay of Lead with Potassium Dichromate Solution......Page 286
Part lV Optical Methods......Page 288
18.1 Introduction......Page 290
18.2 Theory......Page 291
18.3 Instrumentation......Page 293
18.4 Determination of Refractive Index of Pharmaceutical Substances......Page 295
18.5 Applications of Refractivity......Page 296
19.1 Introduction......Page 299
19.2 Theory......Page 300
19.3 Instrumentation......Page 302
19.4.1 Determination of Optical Rotation of Pharmaceutical Substances......Page 303
19.4.2 Determination of Specific Optical Rotation of Pharmaceutical Substances......Page 304
20.1 Introduction......Page 308
20.3.1 Instruments for Nephelometry......Page 309
20.4.1 Turbidimetric Assay
......Page 312
20.4.2 Nephelometric Assay......Page 314
21.2.1 Electromagnetic Spectrum......Page 318
21.2.2 Schematic Representation of Electromagnetic Spectrum
......Page 319
21.2.3 Molar Absorptivity......Page 320
21.2.5 Spectral Presentation......Page 321
21.2.6 Structural Features......Page 322
21.2.7 Absorption of Radiant Energy by Molecules......Page 323
21.2.8 Factors Influencing Absorption of Radiant Energy......Page 326
21.3.1 Single Beam Spectrophometer
......Page 328
21.3.2 Double Beam Spectrophometer
......Page 329
21.4.2 Spectrophotometers......Page 331
21.4.5 Examples......Page 332
21.4.6 UV-Absorption Characteristics of Some Official Pharmaceutical Substances......Page 336
22.1 Introduction......Page 339
22.2.1 Molecular Vibrations......Page 340
22.2.2 Factors Influencing Vibrational Frequencies......Page 343
22.3 Instrumentation......Page 348
22.3.1 Single Monochromator Infrared Spectrophotometers......Page 349
22.3.2 Double Monochromator Infrared Spectrophotometer......Page 351
22.4.1 Applications of IR-Spectroscopy in the Analysis of Pharmaceutical Substances......Page 355
22.4.2 Applications of IR-Spectroscopy in the Analysis of Pharmaceutical Dosage Forms......Page 356
22.5.2 To Distinguish and Characterize the Pri......Page 358
22.5.5 IR-Spectroscopy in the Identification of Functional Groups......Page 359
22.5.7 Interpretation of an IR-Spectrum......Page 360
23.1 Introduction......Page 364
23.1.1 The NMR Phenomenon......Page 365
23.1.2 Informations Provided by 'H-NMR (Proton-NMR)......Page 366
23.2 Theory......Page 367
23.2.2 Precessional Frequency (v)......Page 368
23.2.5 Chemical Shift......Page 369
23.2.6 Spin-Spin Interactions......Page 370
23.2.7 3H-NMR (Tritium NMR-Spectroscopy......Page 372
23.2.8 13C-NMR-Spectroscopy......Page 373
23.2.9 2D-NMR (Two Dimensional Correlation Spectroscopy or Two Dimensional Cosy Spectrum)......Page 374
23.3 Interpretation of a NMR-Spectrum......Page 375
23.3.4 Coupling Constant (J)......Page 376
23.4 Instrumentation......Page 377
23.5.2 Assay of Drugs......Page 378
24.2 Theory......Page 382
24.3.1 Excitation Sources......Page 386
24.3.2 Electrodes......Page 388
24.3.4 Monochromators......Page 389
24.3.5 Detectors......Page 390
24.3.6 Spectrographs......Page 391
24.4 Applications of Emission Spectroscopy......Page 393
25.1 Introduction......Page 395
25.2 Theory......Page 396
25.3.1 Simple Flame Photometer......Page 397
25.3.2 Internal Standard Flame Photometer
......Page 398
25.4.2 Assay of Barium, Potassium and Sodium in Calcium Acetate......Page 400
25.4.3 Cognate Assays......Page 401
26.1 Introduction
......Page 403
26.2.1 Merits of AAS Over FES......Page 404
26.3.1 Single-Beam Atomic Absorption Spectrophotometer......Page 405
26.3.2 Double-Beam Atomic Absorption Spectrophotometer......Page 407
26.4.1 Analytical Techniques......Page 408
26.4.2 Detection Limit and Sensitivity......Page 409
26.4.3 Interferences......Page 410
26.5.2 Assay of Palladium in Carbenicillin Sodium......Page 412
26.5.3 Cognate Assays......Page 413
Part V Assay Methods Based on Separation Techniques......Page 416
27.1 Introduction
......Page 418
27.2 Theory......Page 419
27.2.1 Error Due to the Volume Change......Page 420
27.2.2 Effectiveness of an Extraction
......Page 421
27.3.1 Effect of Temperature and Inert Solutes......Page 422
27.3.2 Effect of ph on Extraction......Page 423
27.3.3 Effect of Ion-Pair Formation......Page 424
27.3.4 Effect of Synergistic Extraction......Page 425
27.4 Emulsion Problem Encountered in Extractions......Page 426
27.5.2 Determination of Iron (lIl) as the 8-Hydroxy Quinolate Complex [Iron (lll) Oxinate]
......Page 428
27.5.3 Determination of Lead (l) by the Dithizone Method......Page 429
27.5.4 Determination of Molybdenum (Vl) by the Thiocyanate Method......Page 430
27.5.5 Determinations of Nickel (ll)......Page 431
28.1 Introduction......Page 434
28.2.1 Versatility of TLC Over Paper and Column Chromatography......Page 435
28.3.1 Preparation of Thin Layers on Plates
......Page 436
28.3.2 Choice of Adsorbents......Page 438
28.3.3 Choice of Solvent System in TLC......Page 440
28.3.5 Purification of Silica Gel-G Layers......Page 442
28.3.7 Development of Thin Layers......Page 443
28.3.8 Special Techniques in TLC......Page 444
28.3.9 Chemical Reactions on TLC Plates......Page 447
28.3.11 Detection of Components......Page 448
28.3.12 Evaluation of the Chromatogram......Page 449
28.4.1 Presence of Specific Substances as Impurities in Drug Substances......Page 450
28.4.2 Related Substances Present in Official Drugs......Page 452
28.4.4 Foreign Steroids Present in Steroidal Drugs......Page 453
28.4.5 Ninhydrin Positive Substances Present in Official Amino Acids......Page 454
29.1 Introduction......Page 456
29.2.1 Plate Theory......Page 457
29.2.2 Rate Theory......Page 458
29.2.3 Random Walk and Nonequilibrium Theory
......Page 459
29.3 Instrumentation......Page 460
29.3.2 Sample Injection System......Page 461
29.3.5 Detectors......Page 462
29.3.7 Integrator......Page 466
29.4 Working Techniques for Quantitative Analysis
......Page 467
29.4.1 Area Normalization......Page 468
29.4.2 Internal Standard Method......Page 469
29.5 Applications of GLC in Pharmaceutical Analysis......Page 470
29.5.1 Assay of Drugs......Page 471
29.5.2 Determination of Specific Organic Compounds as Impurities in Official Pharmaceutical Substances......Page 472
29.5.3 Determination of Related Substances in Official Drugs......Page 473
29.5.5 Determination of Chloroform in Colchicine by Head-Space Gas Chromatography
......Page 474
30.1 Introduction......Page 477
30.2 Theory......Page 478
30.3 Instrumentation......Page 480
30.3.2 Pressure, Flow and Temperature......Page 481
30.3.3 Pumps and Sample Injection System......Page 482
30.3.4 Columns......Page 485
30.3.5 Detectors......Page 486
30.3.6 Strip Chart Recorder......Page 490
30.4.1 Pre-Column Off-Line Derivatization......Page 491
30.4.3 Reagents for Derivatization......Page 492
30.5.2 Control of Microbiological Processes......Page 493
30.5.3 Assay of Cephalosporins......Page 494
30.5.4 Assay of Frusemide**
......Page 495
30.5.5 Assay of Theophylline......Page 496
30.5.6 Assay of Corticosteroids......Page 497
30.5.9 Cognate Assays......Page 498
31.1 Introduction......Page 501
31.2 Theory......Page 502
31.2.3 Materials......Page 503
31.3.2 Detection and Recording......Page 504
31.4.3 Corticotrophin: For Impurities of Higher Molecular Weights......Page 505
31.4.6 Plasma Protein Solution......Page 506
Part Vl Miscellaneous Assay Methods......Page 508
32.1 Introduction......Page 510
32.2 Theory......Page 511
32.2.2 Importance of Antigenic Determinants
......Page 512
32.2.3 Analysis by Competitive Antibody Binding or Isotopically Labelled Compounds
......Page 513
32.3.2 Radioactive Counters
......Page 516
32.5 Applications of Radioimmunoassay (RIA) in Pharmaceutical Analysis
......Page 517
32.5.1 Radioimmunoassay of Morphine
......Page 518
32.5.2 Radioimmunoassay of Hydromorphone and Hydrocodone in Human Plasma......Page 519
32.5.3 Radioimmunoassay of Clonazepam......Page 520
32.5.4 Radioimmunoassay of Flurazepam in Human Plasma
......Page 521
32.5.5 Radioimmunoassay of Chlordiazepoxide in Plasma......Page 522
32.5.6. Radioimmunoassay of Barbiturates
......Page 524
32.5.7 Radioimmunoassay of Flunisolide in Human Plasma
......Page 525
32.6.1 Combined Ria-Techniques Isotope Dilution
......Page 527
32.6.2 Stereospecificity......Page 528
Index......Page 535
