Identification and determination of impurities in drugs:
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| Main Author: | |
|---|---|
| Format: | Book |
| Language: | English |
| Published: |
Amsterdam [u.a.]
Elsevier
2000
|
| Edition: | 1. ed. |
| Series: | Progress in pharmaceutical and biomedical analysis
4 |
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | XXIII, 748 S. Ill., graph. Darst. |
| ISBN: | 0444828990 |
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| 245 | 1 | 0 | |a Identification and determination of impurities in drugs |c ed. by Sándor Görög |
| 250 | |a 1. ed. | ||
| 264 | 1 | |a Amsterdam [u.a.] |b Elsevier |c 2000 | |
| 300 | |a XXIII, 748 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
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| 338 | |b nc |2 rdacarrier | ||
| 490 | 1 | |a Progress in pharmaceutical and biomedical analysis |v 4 | |
| 650 | 4 | |a Chimie pharmaceutique | |
| 650 | 2 | |a Contamination médicamenteuse | |
| 650 | 4 | |a Médicaments - Analyse | |
| 650 | 7 | |a Médicaments - Analyse |2 ram | |
| 650 | 4 | |a Pharmacologie | |
| 650 | 2 | |a Préparations pharmaceutiques - analyse | |
| 650 | 4 | |a Chemistry Techniques, Analytical | |
| 650 | 4 | |a Contamination (Technology) | |
| 650 | 4 | |a Drug Contamination | |
| 650 | 4 | |a Drug adulteration | |
| 650 | 4 | |a Drugs |x Analysis | |
| 650 | 4 | |a Pharmaceutical Preparations |x analysis | |
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| adam_text | Contents
Preface v
List of contributors xxi
1. Various aspects of the estimation of impurities in drugs
1.1. Introductory remarks 1
S. Gorog
1.1.1. Drug purity and the safety of drug therapy 1
1.1.2. Aims and scope 6
References 7
1.2. The nature and origin of the impurities in drug substances 9
S. Gorog
1.2.1. Organic impurities 9
1.2.1.1. Last intermediate of the synthesis 9
1.2.1.2. Products of incomplete reaction during the
synthesis 10
1.2.1.3. Products of overreaction 11
1.2.1.4. Impurities originating from impurities in the
starting material of the synthesis 12
1.2.1.5. Impurities originating from the solvent of the
reaction 13
1.2.1.6. Impurities originating from the catalyst 14
1.2.1.7. Products of side reactions 14
1.2.1.8. Degradation products as impurities 16
1.2.1.9. Enantiomeric impurities 16
1.2.2. Residual solvents 17
1.2.3. Inorganic impurities 18
1.2.4. Impurities in excipients 19
References 21
1.3. Toxicological aspects 23
R. Lee
1.3.1. Introduction 23
1.3.1.1. Biological pharmaceuticals 26
1.3.2. Impurities closely related chemically to the active
substance 26
1.3.2.1. Biological pharmaceuticals 28
viii
1.3.3. Impurities less closely related in structure to the active
substance 29
1.3.3.1. Biological pharmaceuticals 29
1.3.4. Impurities of known structure, not related chemically to
active substance 30
1.3.4.1. Biological pharmaceuticals 31
1.3.4.2. Excipients 31
1.3.5. Impurities of unknown structure 32
1.3.6. Best use of resources 33
1.3.6.1 The toxicity testing programme 34
1.3.7. Concluding commentary 35
References 36
1.4. The role of impurity profiling in drug research, development and
production 38
S. Gorog
1.4.1. Impurity profiling in synthetic drug research 38
1.4.2. Impurity profiling in the production of bulk drugs 40
1.4.3. Impurity profiling in the research and production of drug
formulations 41
1.4.4. Impurity profiles in drug registration: legal aspects 43
References 46
1.5. Regulatory aspects: ICH and pharmaeopoeial perspectives 48
J.P Boehlert
1.5.1. Introduction 48
1.5.2. International Conference on Harmonisation (ICH) 48
1.5.2.1. Process 48
1.5.2.2. ICH topics 49
1.5.3. ICH Impurity Guidelines for New Drug Substances and
New Dosage Forms 49
1.5.3.1. Introduction 49
1.5.3.2. Classification of impurities 50
1.5.3.3. Reporting and control of impurities in the
registration applications 51
1.5.3.4. Qualification of impurities 54
1.5.3.5. New impurities 57
1.5.4. ICH residual solvents guideline 57
1.5.4.1. Introduction 57
1.5.4.2. Classification of residual solvents 58
1.5.4.3. Analytical procedures 58
1.5.4.4. Testing 60
1.5.4.5. Setting limits 61
1.5.4.6. Reporting levels of residual solvents 61
ix
1.5.5. Pharmacopoeial treatment of impurities 62
1.5.6. The United States Pharmacopoeia (USP) 62
1.5.6.1. Introduction 62
1.5.6.2. Ordinary impurities 62
1.5.6.3. Impurities in official articles 62
1.5.6.4. Organic volatile impurities (OVIs) 63
1.5.6.5. Other impurities 63
1.5.7. European Pharmacopoeia (Ph. Eur.) 64
1.5.7.1. Introduction 64
1.5.7.2. General notices 64
1.5.7.3. General chapters 65
1.5.7.4. Related substances 65
References 65
2. Identification, structure elucidation and determination of related organic
impurities
2.1. Strategies in impurity profiling 67
S. Gorog
2.1.1. General considerations 67
2.1.2. Detection of impurities 71
2.1.3. Attempted identification of impurities by chromato
graphic retention matching with known potential
impurities 72
2.1.4. Complex application of chromatographic, spectroscopic
and hyphenated techniques for the structure elucidation
of impurities 73
2.1.5. Synthesis of the impurities 76
2.1.6. Quantitative determination of the impurities 78
2.1.7. A case study: structure elucidation of two impurities
in norgestrel 79
References 82
2.2. UV VIS spectroscopy and fluorimetry 84
S. Gordg
2.2.1. Applications without chromatographic separation 84
2.2.1.1. Methods based on natural UV absorption 84
2.2.1.2. Methods based on colour reactions 90
2.2.1.3. Fluorimetric methods 93
2.2.2. Applications after chromatographic separation 93
References 95
2.3. Mass spectrometry in impurity profiling 97
M. Mak, G. Czira, J. Brlik
X
2.3.1. Introduction 97
2.3.2. Applications without chromatographic separation 98
2.3.3. Applications after chromatographic separation 103
References 107
2.4. NMR spectroscopv 109
C s. Szantay Jr., A. Demeter
2.4.1. Introduction 109
2.4.2. NMR as a structure elucidation uh I 110
2.4.3. The sensitivity problem 114
2.4.4. NMR as a quantification tool 118
2.4.5. Application of NMR in drug impurity profiling after
chromatographic separation 121
2.4.6. Applications of NMR without chromatographic
separation 122
2.4.7. Hxamples 123
2.4.7.1. Impurity profiling of enalapril and lisinopril 123
2.4.7.2. Structural elucidation of two novel ergot
alkaloid impurities in u ergocryptine and
bromocryptine 133
2.4.7.3. C imetidine impurities 135
References 141
2.5. Planar chromatography 146
K. Ferenczi Fodor, Z. Vegh
2.5.1. Introduction 146
2.5.2. Planar chromatography in pharmacopoeias 148
2.5.3. Semiquantitative planar chromatography (advantages
and disadvantages) 149
2.5.4. Quantitative planar chromatography,
UV/VIS densitomelry 153
2.5.5. Other detection modes 160
2.5.5.1. Fluorodensitometry 160
2.5.5.2. In situ TLC Fourier transform infrared (FTIR)
spectroscopy 162
2.5.5.3. Planar chromatography coupled with mass
spectrometry 165
2.5.6. Special techniques: programmed multiple development
and automated multiple development 167
2.5.7. Overpressured layer chromatography 169
2.5.8. Validation of the planar chromatographic purity tests 176
References 179
2.6. Gas chromatography (GC) and related techniques 183
A. Lauko
xi
2.6.1. Limitations in the applicability of GC for impurity
profiling: derivatisation 183
2.6.2. Selection of columns for the separation of impurities by
GC 185
2.6.3. Sample introduction systems 188
2.6.4. Detectors 189
2.6.4.1. General considerations 189
2.6.4.2. Flame ionisation detector (FID) 190
2.6.4.3. Electron capture detector (ECD) 190
2.6.4.4. Mass selective detector (MSD) 191
2.6.5. Temperature programming 193
2.6.6. Qualitative analysis by GC/MS: identification and
structure elucidation of impurities 194
2.6.7. Quantitative determination of impurities 202
References 206
2.7. High performance liquid chromatography (HPLC) and related
techniques 210
2.7.1. Separation, detection and determination of impurities by
HPLC 210
M. Gazdag
2.7.1.1. Introduction 210
2.7.1.2. Column and system selection for the separa¬
tion of impurities by HPLC 211
2.7.1.3. System optimisation 213
2.7.1.4. Detection problems (selectivity and sensitiv¬
ity) 217
2.7.1.5. Quantitative determination and method vali¬
dation of impurities by HPLC 222
2.7.1.6. HPLC purity tests in modern pharmaceutical
analysis: pharmacopoeial aspects 231
References 236
2.7.2. Isolation of impurities by (semi)preparative HPLC 240
A. Aranyi
2.7.2.1. Introduction 240
2.7.2.2. Definition of the task. Data collection 240
2.7.2.3. Selection of the starting material 241
2.7.2.4. Elaboration of isolation strategy: development
of preparative HPLC methods 242
2.7.2.5. Performing the isolation 245
2.7.2.6. Analysis of the isolated impurity 245
2.7.2.7 . A case study: isolation of two unknown
impurities in bromocryptine 245
xii
References 250
2.7.3. The role of the diode array UV spectra in the identifi¬
cation of impurities 252
S. Gorog
2.7.3.1. General considerations 252
2.7.3.2. Practical examples 256
References 264
2.7.4. HPLC/MS for drug impurity identification 266
L. Tollsten
2.7.4.1. Introduction 266
2.7.4.2. History and development of HPLC/MS inter¬
faces 266
2.7.4.3. Mass analysers for HPLC/MS 267
2.7.4.4. Optimisation of reversed phase HPLC/MS
(buffers, pH, organic solvents, adducts and
ion pairing agents) 269
2.7.4.5. Straight phase HPLC/MS 274
2.7.4.6. Micro column HPLC/MS 275
2.7.4.7. Flow injection MS 277
2.7.4.8. Peak purity determination by HPLC/MS 279
2.7.4.9. Hydrogen deuterium exchange 280
2.7.4.10. HPLC/MS/MS 282
2.7.4.11. High resolution MS and MS/MS 288
2.7.4.12. Sample preparation 290
2.7.4.13. Fraction collection 291
2.7.4.14. Notes on HPLC/APCI MS 293
2.7.4.15. Impurities in drug formulations 293
2.7.4.16. Conclusions 296
References 296
2.7.5. HPLC/NMR and related hyphenated NMR methods 299
I.D. Wilson, L. Griffiths, J.C. Lindon, J.K. Nicholson
2.7.5.1. Introduction 299
2.7.5.2. Development of HPLC/NMR 299
2.7.5.3. Suitable nuclei for HPLC/NMR 303
2.7.5.4. Experimental aspects of HPLC/NMR 303
2.7.5.5. Strategies for the use of HPLC/NMR for
impurity profiling 306
2.7.5.6. Applications of HPLC/NMR to impurity
profiling 308
2.7.5.7. Future approaches to impurity profiling ((CE/
CEC)/NMR, SFC/NMR, HPLC/NMR/MS) 317
2.7.5.8. Conclusions 320
xiii
References 320
2.8. Determination of drug related impurities by capillary electro
phoresis 323
K.D. Altria
2.8.1. Introduction to capillary electrophoresis (CE) 323
2.8.2. Pharmaceutical analysis by CE 326
2.8.3. Related impurities determinations by CE 327
2.8.4. Separations using low pH electrolytes 329
2.8.5. HighpH 334
2.8.6. Micellar electrokinetic capillary chromatography
(MECC) 336
2.8.7. Microemulsion CE 338
2.8.8. Non aqueous CE 339
2.8.9. Indirect UV detection applications 340
2.8.10. Comparison of CE performance with HPLC 342
2.8.11. CE/MS 343
References 343
2.9. Capillary electrochromatography (CEC) 346
2.9.1. Separation, detection and determination of impurities by
CEC 346
M.R. Euerby
2.9.1.1. Introduction 346
2.9.1.2. Analysis of neutral and ion suppressed phar
maceuticals 347
2.9.1.3. Analysis of acidic Pharmaceuticals 347
2.9.1.4. Analysis of pharmaceutical bases 348
2.9.1.5. Analysis of mixtures containing acids, bases
and neutrals 349
2.9.1.6. Detection considerations 349
2.9.1.7. Selected examples of the determination of
impurities by CEC 351
References 357
2.9.2. CEC/MS 359
S.L. Lane
2.9.2.1. Introduction 359
2.9.2.2. Development of CEC/MS 361
2.9.2.3. Performance 366
2.9.2.4. Method development 367
2.9.2.5. Applications 370
2.9.2.6. Reduction of analysis times and automation 375
2.9.2.7. Conclusion and future 380
References 380
xiv
2.10. Supercritical fluid chromatography (SFC) 382
0. Gyllenhaall
2.10.1. Introduction to SFC 382
2.10.2. SFC using capillary columns 382
2.10.3. SFC using packed columns 383
2.10.4. SFC/MS using packed columns 389
2.10.5. Other detectors used for the structural elucidation of
unknowns in SFC 391
2.10.6. Analysis of enantiomeric purity 391
2.10.7. Advantages and limitations of SFC in the purity analysis
of drugs 392
References 394
2.11. Purity check by differential scanning calorimetry 396
1. Peter
References 399
3. Identification and determination of residual solvents
3.1. Thermoanalytical methods 401
I. Peter
References 407
3.2. Gas chromatography and GC/MS 409
J. Bertram
3.2.1. Introduction 409
3.2.2. General points valid for the GC determination of
residual solvents 410
3.2.3. Sample pretreatment 410
3.2.3.1. Direct Injection 410
3.2.3.2. Static headspace (HS) 413
3.2.3.3. Multiple headspace extraction (MHE) 417
3.2.3.4. Full evaporation technique (FET) 419
3.2.3.5. Dynamic headspace 419
3.2.3.6. Thermal desorption 424
3.2.3.7. Solid phase micro extraction (SPME) 425
3.2.4. Column choice for GC separation of solvents 426
3.2.5. Temperature program 427
3.2.6. Detection and identification 427
3.2.6.1. Two column approach 427
3.2.6.2. GC/MS 429
3.2.6.3. Membrane inlet mass spectrometry 437
References 439
3.3. NMR spectroscopy 441
G. Balogh
XV
References 447
3.4. Miscellaneous 448
S. Gorog
References 449
4. Identification, semiquantitative and quantitative determination of inorganic
impurities
4.1. Classical methods 451
S. Gorog
4.1.1. General remarks 451
4.1.2. Residue on ignition 452
4.1.3. Chloride 452
4.1.4. Fluoride 452
4.1.5. Sulphate 453
4.1.6. Phosphate 453
4.1.7. Sulphite 453
4.1.8. Heavy metals 454
4.1.8.1. General method 454
4.1.8.2. Lead 454
4.1.8.3. Iron 454
4.1.8.4. Mercury 454
4.1.9. Other metals 455
4.1.9.1. Potassium 455
4.1.9.2. Alkaline earth metals 455
4.1.9.3. Aluminium 455
4.1.10. Arsenic 455
4.1.11. Miscellaneous 456
References 456
4.2. Atomic spectroscopy 458
A. Lasztity
4.2.1. Introduction 458
4.2.2. Palladium 458
4.2.3. Nickel 460
4.2.4. Lead 461
4.2.5. Multielement determinations 462
4.2.6. Other metals and elements 464
References 465
4.3. Other methods 468
S. Gorog
4.3.1. Electroanalytical methods 468
4.3.2. Ion chromatography 468
xvi
4.3.3. Capillary ion electrophoresis 469
References 471
5. Degradation products as impurities
S. Gorog
5.1. The relation between drug stability studies and the estimation of
impurity profiles 473
References 476
5.2. Aims, forms and conditions of drug stability testing 477
References 478
5.3. Elucidation of degradation pathways 480
5.3.1. Introduction 480
5.3.2. The use of HPLC/diode array UV spectra 480
5.3.3. The use of mass spectrometry in association with
separation techniques 483
5.3.4. The complex application of chromatographic and spec
troscopic techniques 488
5.3.5. Special problems of drug dosage forms 493
References 494
5.4. Elucidation of light induced degradation pathways 497
5.4.1. The importance of photodegradation studies 497
5.4.2. Classical examples 498
5.4.3. Recent studies for the elucidation photodegradation
pathways 499
References 504
5.5. Methodological aspects of quantitative drug stability studies
based on degradates 506
5.5.1. General remarks 506
5.5.2. Spectrophotometric and spectroscopic studies 506
5.5.3. HPLC studies 508
5.5.4. Gas chromatographic studies 515
5.5.5. Thin layer chromatographic studies 516
5.5.6. Capillary electrophoretic studies 520
References 522
6. Estimation of enantiomeric impurities
6.1. Introduction 525
S. Gorog
References 527
6.2. Chromatographic methods 528
S. Gorog
xvii
6.2.1. Separation after chiral covalent derivatisation 528
6.2.2. Separation on achiral columns using homochiral mobile
phase additives 531
6.2.3. Direct separation on chiral columns 533
References 538
6.3. Capillary electrophoretic (CE) methods 540
J. Crommen
6.3.1. Introduction 540
6.3.2. CE mode and type of chiral selector 540
6.3.3. Quantitative aspects and method validation 544
6.3.4. Applications to enantiomeric purity testing 547
References 550
6.4. Polarimetry, ORD and CD spectroscopy 553
A. Gergely
6.4.1. Introduction 553
6.4.2. Determination of enantiomeric purity by the direct
application of ORD and CD spectroscopy 554
6.4.3. The use of chiroptical HPLC detectors for the analysis of
enantiomeric purity 556
6.4.4. Conclusions 559
References 559
6.5. NMR spectroscopy 562
G. Tarkanyi
6.5.1. Introduction 562
6.5.2. Chiral solvent additives 565
6.5.3. Cyclodextrins (Cds) as chiral solvating agents 566
6.5.4. Application of lanthanide shift reagents (LSR) 569
6.5.5. Chiral NMR solovents 570
6.5.6. Multinuclear approach 571
6.5.7. Conclusions 571
References 572
7. Estimation of polymorphic modifications as impurities in drugs
7.1. The phenomenon and importance of polymorphism 575
B. Hegedus
7.1.1. Introduction 575
7.1.2. Polymorphism among the drug substances 576
7.1.2.1. Bioavailability 576
7.1.2.2. Pharmaco technological characteristics 577
7.1.2.3. Manufacturing technological parameters 577
7.1.3. Methods for morphological examinations 578
xviii
References 578
7.2. Infrared and Raman spectroscopy 580
B. Hegedus
7.2.1. Introduction 580
7.2.2. FT IR measurements 580
7.2.2.1. Standard FT IR spectroscopy 580
7.2.2.2. Other techniques 582
7.2.3. FT Raman measurements 583
7.2.4. Quantitative determination of morphological impurities 586
7.2.4.1. Measurements based on well resolved bands 586
7.2.4.2. Measurements using spectrum manipulations 587
7.2.4.3. Evaluation of complete spectrum curves with
mathematical methods 589
References 590
7.3. Thermoanalytical methods 592
I. Peter
7.3.1. General considerations 592
7.3.2. Estimation of lower melting form (B) in higher melting
form (A) on the basis of solid solid transformation 596
7.3.3. Estimation of lower melting form (B) and higher melting
form (A) on the basis of their fusions 596
References 599
7.4. X ray crystallography 601
M. Balint
7.4.1. The role of X ray diffraction methods in morphological
studies 601
7.4.2. Determination of polymorphic impurities with X ray
diffraction 602
References 606
8. Microbiological examination of non sterile drugs and raw materials
H. Van Doorne
8.1. Introductory remarks 609
8.2. Validation 612
8.2.1. General aspects of validation 612
8.2.2. Validation of total viable count 616
8.2.3. Validation of test for specified micro organisms 616
8.3. Total viable count 618
8.3.1. Preparation of the sample 618
8.3.2. Test procedures 621
8.4. Tests for specified organisms 623
8.4.1. Introduction 623
xix
8.4.2. Enterobacteriaceae 624
8.4.3. Escherichia coli 626
8.4.4. Salmonella 627
8.4.5. Pseudomonas aeruginosa 630
8.4.6. Staphylococcus aureus 632
8.4.7. Clostridium 633
8.5. Concluding remarks 633
References 634
9. Selected examples (impurity profiling of some groups of drugs)
9.1. Peptides 639
S. Gorog
9.1.1. Methodological aspects 639
9.1.2. Synthesis related impurities 641
9.1.3. Enantiomeric and diastereomeric impurities 650
9.1.4. Degradation products 653
References 657
9.2. Biotechnological products 660
K. Ganzler, A.S. Cohen
9.2.1. Introduction 660
9.2.2. Therapeutic proteins 661
9.2.2.1. General considerations 661
9.2.2.2. Non proteinaceous contaminants 662
9.2.2.3. Extraneous protein contaminants 666
9.2.2.4. Contaminants of target protein origin 666
9.2.3. Oligonucleotides 678
References 681
9.3. Antibiotics 684
A. Van Schepdael, E. Adams, E. Roets, J. Hoogmartens
9.3.1. Introduction: official methods for analysis of
antibiotics 684
9.3.2. Penicillins 687
9.3.3. Cephalosporins 691
9.3.4. Macrolides 692
9.3.5. Tetracyclines 697
9.3.6. Aminoglycosides 698
9.3.7. Polypeptides 703
9.3.8. Polyenes 704
References 705
9.4. Steroids 712
S. Gorog
9.4.1. Methodological aspects 712
xx
9.4.2. Selected examples of synthesis related impurities 716
9.4.2.1. Total synthesis 716
9.4.2.2. Birch reduction of the phenolic ring A 719
9.4.2.3. Ethinylation of the 17 oxo group 721
9.4.2.4. Introduction of fluorine 724
9.4.2.5. Microbiological oxidation 725
9.4.3. Degradation products 726
References 729
Subject index 733
|
| any_adam_object | 1 |
| author | Görög, Sándor 1933- |
| author_GND | (DE-588)152433287 |
| author_facet | Görög, Sándor 1933- |
| author_role | aut |
| author_sort | Görög, Sándor 1933- |
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| building | Verbundindex |
| bvnumber | BV013366035 |
| callnumber-first | R - Medicine |
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| callnumber-raw | RS189 |
| callnumber-search | RS189 |
| callnumber-sort | RS 3189 |
| callnumber-subject | RS - Pharmacy |
| classification_rvk | VS 5300 |
| ctrlnum | (OCoLC)43905893 (DE-599)BVBBV013366035 |
| dewey-full | 615/.1901 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 615 - Pharmacology and therapeutics |
| dewey-raw | 615/.1901 |
| dewey-search | 615/.1901 |
| dewey-sort | 3615 41901 |
| dewey-tens | 610 - Medicine and health |
| discipline | Chemie / Pharmazie Medizin |
| edition | 1. ed. |
| format | Book |
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| id | DE-604.BV013366035 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T18:44:34Z |
| institution | BVB |
| isbn | 0444828990 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-009117181 |
| oclc_num | 43905893 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR DE-20 |
| owner_facet | DE-355 DE-BY-UBR DE-20 |
| physical | XXIII, 748 S. Ill., graph. Darst. |
| publishDate | 2000 |
| publishDateSearch | 2000 |
| publishDateSort | 2000 |
| publisher | Elsevier |
| record_format | marc |
| series | Progress in pharmaceutical and biomedical analysis |
| series2 | Progress in pharmaceutical and biomedical analysis |
| spelling | Görög, Sándor 1933- Verfasser (DE-588)152433287 aut Identification and determination of impurities in drugs ed. by Sándor Görög 1. ed. Amsterdam [u.a.] Elsevier 2000 XXIII, 748 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Progress in pharmaceutical and biomedical analysis 4 Chimie pharmaceutique Contamination médicamenteuse Médicaments - Analyse Médicaments - Analyse ram Pharmacologie Préparations pharmaceutiques - analyse Chemistry Techniques, Analytical Contamination (Technology) Drug Contamination Drug adulteration Drugs Analysis Pharmaceutical Preparations analysis Pharmazeutische Analyse (DE-588)4174139-0 gnd rswk-swf Arzneimittel (DE-588)4003115-9 gnd rswk-swf Verunreinigung (DE-588)4188107-2 gnd rswk-swf Arzneimittel (DE-588)4003115-9 s Verunreinigung (DE-588)4188107-2 s Pharmazeutische Analyse (DE-588)4174139-0 s DE-604 Progress in pharmaceutical and biomedical analysis 4 (DE-604)BV010273310 4 HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009117181&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Görög, Sándor 1933- Identification and determination of impurities in drugs Progress in pharmaceutical and biomedical analysis Chimie pharmaceutique Contamination médicamenteuse Médicaments - Analyse Médicaments - Analyse ram Pharmacologie Préparations pharmaceutiques - analyse Chemistry Techniques, Analytical Contamination (Technology) Drug Contamination Drug adulteration Drugs Analysis Pharmaceutical Preparations analysis Pharmazeutische Analyse (DE-588)4174139-0 gnd Arzneimittel (DE-588)4003115-9 gnd Verunreinigung (DE-588)4188107-2 gnd |
| subject_GND | (DE-588)4174139-0 (DE-588)4003115-9 (DE-588)4188107-2 |
| title | Identification and determination of impurities in drugs |
| title_auth | Identification and determination of impurities in drugs |
| title_exact_search | Identification and determination of impurities in drugs |
| title_full | Identification and determination of impurities in drugs ed. by Sándor Görög |
| title_fullStr | Identification and determination of impurities in drugs ed. by Sándor Görög |
| title_full_unstemmed | Identification and determination of impurities in drugs ed. by Sándor Görög |
| title_short | Identification and determination of impurities in drugs |
| title_sort | identification and determination of impurities in drugs |
| topic | Chimie pharmaceutique Contamination médicamenteuse Médicaments - Analyse Médicaments - Analyse ram Pharmacologie Préparations pharmaceutiques - analyse Chemistry Techniques, Analytical Contamination (Technology) Drug Contamination Drug adulteration Drugs Analysis Pharmaceutical Preparations analysis Pharmazeutische Analyse (DE-588)4174139-0 gnd Arzneimittel (DE-588)4003115-9 gnd Verunreinigung (DE-588)4188107-2 gnd |
| topic_facet | Chimie pharmaceutique Contamination médicamenteuse Médicaments - Analyse Pharmacologie Préparations pharmaceutiques - analyse Chemistry Techniques, Analytical Contamination (Technology) Drug Contamination Drug adulteration Drugs Analysis Pharmaceutical Preparations analysis Pharmazeutische Analyse Arzneimittel Verunreinigung |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009117181&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| volume_link | (DE-604)BV010273310 |
| work_keys_str_mv | AT gorogsandor identificationanddeterminationofimpuritiesindrugs |