Handbook of Drug Analysis Applications in Forensic and Clinical Laboratories

by Liu, Ray H.; Gadzala, Daniel E.

• ISBN13: 9780841234482
• ISBN10: 0841234485
• Format: Hardcover
• Copyright: 1997-05-05
• Publisher: American Chemical Society

Summary

Covers preliminary test and chromatographic methods in forensic drug testing. Reviews identification methods such as molecular spectrophotometry, nuclear magnetic resonance, and mass spectrometry. Discusses the fundamental relationship between instrumentation and drug analysis. Evaluates the characteristics and pretreatment approaches for common sample categories. Presents in-depth test result interpretation on issues commonly encountered in workplace drug urinalysis. Analyzes and compares performance characteristics of immunoassays commonly used for workplace drug urinalysis.

Table of Contents

Dedication	iii	(2)
Foreword	v	(2)
Preface	vii	(2)
About the Authors	ix	(10)
Introduction	xix
SECTION I NATURE OF DRUG ABUSE AND SAMPLE CHARACTERISTICS AND PRETREATMENT	3	(54)
Chapter 1. Nature of Abused Drugs and Sample Characteristics	3	(32)
Drug Abuse and Drug Testing	3	(3)
Assessing the Extent of Drug Use	3	(1)
Evolution of the Nation's Antidrug Policy	4	(1)
The Response and Contribution of the Scientific Communities: Drug Testing	4	(2)
Drug Classification	6	(2)
Chemical Structure	7	(1)
Legal Schedule	7	(1)
Pharmacological Effect	8	(1)
Samples in Criminal Investigations	8	(6)
Illicit Solid Dosage Forms	8	(6)
Carriers	9	(1)
Unintended Impurities	9	(2)
Intended Combinations	11	(2)
Multiple Active Ingredients	11	(1)
Excipients and Adulterants	12	(1)
Unexpected Contents	13	(1)
Counterfeits	13	(1)
Look-Alike and Designer Drugs	14	(1)
Biological Samples	14	(15)
Drug Metabolism	14	(5)
Administration, Absorption, Distribution, and Excretion of Drugs	15	(3)
Exposure	17	(1)
Distribution	17	(1)
Excretion	18	(1)
Biotransformation of Drugs	18	(1)
General Drug Biotransformation Patterns	19	(1)
Metabolites of Drugs Commonly Found in Forensic Analysis	19	(1)
Characteristics of Biological Samples	19	(10)
Biological Fluids	21	(2)
Blood, Plasma, and Serum	22	(1)
Urine	22	(1)
Saliva	22	(1)
Postmortem Tissues	23	(3)
Vitreous Humor	24	(1)
Liver	25	(1)
Brain	25	(1)
Stomach Contents	26	(1)
Bile	26	(1)
Muscle	26	(1)
Unconventional Samples	26	(3)
Hair	26	(2)
Sweat	28	(1)
Bone, Nails, and Biological Stains	28	(1)
Meconium	29	(1)
Insect Larvae	29	(1)
References	29	(6)
Chapter 2. Sample Pretreatment	35	(22)
Extraction of Drugs in Dosage Forms	35	(3)
pH Adjustment	35	(1)
Extraction Efficiency	36	(1)
Specific Applications	36	(2)
Extraction of Drugs in Plant Materials	38	(1)
Pretreatment of Biological Samples	38	(13)
Acid and Enzyme Hydrolysis of Conjugated Drugs	39	(1)
Protein Removal	40	(1)
Inorganic Acids and Salts	40	(1)
Organic Solvent Precipitation	40	(1)
Proteolytic Enzymes	41	(1)
Extraction	41	(10)
Liquid-Liquid Extraction of Organic-Solvent-Soluble Drugs	42	(3)
Solvent Selection	42	(2)
Removal or Identification of Co-Extracted Materials	44	(1)
Extraction-Derived Artifacts	44	(1)
Extraction of Water-Soluble Drugs	45	(1)
Liquid-Solid Extraction of a Lyophilized Sample	45	(1)
Ion-Pair Extraction	45	(1)
Salting-Out	45	(1)
Formation of Derivatives Favoring Organic Solvent Extraction	46	(1)
Solid-Phase Extraction	46	(5)
Solid-Phase Adsorbents and Intermolecular Forces	47	(2)
Automation	49	(1)
Application Examples	49	(2)
References	51	(6)
SECTION II PRELIMINARY TEST AND CHROMATOGRAPHIC METHODS	57	(116)
Chapter 3. Color Tests	57	(4)
Comparison of Color Formation with a Color Chart Reference	57	(1)
Multiple Reagent Testing	58	(2)
References	60	(1)
Chapter 4. Thin-Layer Chromatography	61	(12)
TLC Systems	61	(4)
Reproducibility	62	(1)
Correction of Retention Data	62	(1)
Evaluation of System Separation Power	63	(1)
Selection of Developing Systems	63	(2)
Detection	65	(1)
Standardized Operation	65	(5)
References	70	(3)
Chapter 5. Immunoassay	73	(56)
Immunoassay and Workplace Drug Urinalysis	73	(3)
The Basis of Immunoassays	73	(1)
On-Site versus Laboratory-Based Immunoassay Kits	74	(1)
Role of Immunoassay in Workplace Drug Urinalysis	74	(1)
Correlation of Preliminary-Test and Confirmation-Test Results	75	(1)
Methodologies and Cross-Reactivities	76	(26)
Radioimmunoassay	76	(8)
Basic Methodology	76	(1)
Cross-Reactivities	77	(5)
Application and Sample Characteristics	82	(2)
Enzyme Immunoassay	84	(10)
Basic Methodology	84	(3)
Cross-Reactivities	87	(7)
Application and Sample Characteristics	94	(1)
Fluorescence Polarization Immunoassay	94	(1)
Basic Methodology	94	(1)
Cross-Reactivity	95	(1)
Application and Sample Characteristics	96	(5)
Particle Immunoassay	101	(1)
Basic Methodology	101	(1)
Interference	102	(7)
Targeted Analytes Derived from Unintended Exposure, Food Consumption, and Licit Medication	104	(1)
Unknown Cross-Reacting Compounds	104	(1)
Nonspecific Binding	105	(1)
Detection Mechanism	105	(1)
Adulterants	106	(3)
Simultaneous Multiple-Drug Detection	109	(1)
Comparison of Immunoassay Performance Characteristics	110	(11)
Consistency of Immunoassay and GC-MS Test Results	111	(1)
Assay Precision and Sensitivity	111	(2)
Quantitative Data Correlation Between GC-MS and Different Immunoassays	113	(6)
Selection of Samples for Correlation Studies	113	(1)
Cannabinoids	114	(3)
Correlation Studies of Commercial Immunoassays	114	(1)
Interpretation of Correlation Parameters	114	(3)
Cocaine	117	(1)
Opiates	118	(1)
Quantitative Data Correlation of GC-MS and Immunoassays Performed with Reagents Manufactured at Different Time Periods	119	(1)
Selection of Immunoassay Cutoff in Workplace Drug Urinalysis	119	(2)
Development and Comparison of "Quick Test" Immunoassay Kits	121	(3)
References	124	(5)
Chapter 6. Chromatographic Methods	129	(44)
Classification and Complementary Nature of Chromatographic Methods	129	(1)
Operational Characteristics of GC and HPLC	130	(1)
Gas Chromatography	131	(15)
Basic Operational Principles and Parameters	131	(3)
Stationary Phases	132	(1)
Optimization of Analysis--Selection of Column Internal Diameter, Stationary-Phase Film Thickness, Carrier Gas, and Stationary Phases	132	(1)
Optimization of Analysis Speed	132	(2)
Limitations	134	(1)
Chemical Derivatization	134	(7)
Merits of Chemical Derivatization	134	(1)
Compatibility with the Chromatographic Environment	134	(2)
Achieving Required Separation or Improving Separation Efficiency	136	(1)
Improvement of Detection and Structure-Elucidation Efficiency	136	(2)
Chemical-Derivatization Reactions and Practical Considerations	138	(2)
Representative Derivatization Approaches	140	(1)
Retention Data as a Basis for Preliminary Drug Identification	141	(4)
Identification Based on Relative Retention Time Data	141	(1)
Identification Based on Retention Index Data	141	(4)
Comparability of Retention Indices Obtained under Various Conditions	141	(2)
Utilization of Non-Paraffins as References	143	(2)
Detection Systems	145	(1)
Basic Operational Principle	145	(1)
Applications	145	(1)
High-Pressure Liquid Chromatography	146	(19)
Basic Operational Principles and Parameters of HPLC	148	(5)
Solvent Characteristics and Resolution Optimization	149	(3)
Stationary Phase	152	(1)
Retention Data as a Basis for Preliminary Drug Identification	153	(8)
Limited Screening	153	(5)
General Screening	158	(1)
Standardization of Retention Data	158	(3)
Capacity Factor and Relative Adjusted Capacity Factor	158	(1)
Retention Index	159	(1)
Further Improvements	160	(1)
Detection Systems	161	(4)
Absorption	161	(2)
Fluorescence	163	(1)
Electrochemical Detection	164	(1)
References	165	(8)
SECTION III IDENTIFICATION METHODS	173	(74)
Chapter 7. Molecular Spectrophotometry	173	(12)
UV-Visible Spectrophotometry	173	(3)
Correlation of Electronic Absorption Spectra with Molecular Structure	174	(1)
Applications Involving Chemical Derivatization	175	(1)
Extended Techniques and Their Applications	176	(1)
Infrared Spectrophotometry	176	(8)
Basic Operational Parameters	176	(2)
Spectrum-Structure Correlation	178	(3)
Practical Considerations and Spectrometric Examination	181	(1)
Sample Preparation for Spectrometric Examination	181	(1)
Approaches and Cautions for Comparing Unknown Spectra with Known Collections	182	(1)
Other Molecular Spectrophotometry	182	(2)
Fluorescence Spectrophotometry	182	(1)
Circular Dichroism	183	(1)
References	184	(1)
Chapter 8. Nuclear Magnetic Resonance Spectrometry	185	(10)
Magnetic Resonance	185	(1)
Chemical Shift and Spin-Spin Coupling	185	(1)
Proton Nuclear Magnetic Resonance ((1)H NMR)) Spectrometry	186	(5)
(1)H NMR Spectrometry of Commonly Abused Drugs	186	(2)
Differentiation of Enantiomers	188	(3)
Carbon-13 Nuclear Magnetic Resonance ((13)C NMR)) Spectrometry	191	(3)
References	194	(1)
Chapter 9. Mass Spectrometry	195	(52)
General Trend and Development	195	(4)
Sample Introduction	196	(1)
Ionization Methods	196	(1)
Recent Developments in MS	197	(1)
Computer Applications: Data Acquisition and Conversion, Data Retrieval, Spectrum Interpretation, Mathematical and Statistical Treatment of MS Data, and Targeted-Compound Analysis	198	(1)
MS Characteristics of Commonly Abused Drugs	199	(23)
Amphetamines and Related Amine Drugs	200	(2)
Morphine and Related Alkaloids	202	(6)
Marijuana and Other Cannabinoid-Containing Materials	208	(3)
Barbiturates	211	(2)
Cocaine	213	(2)
Phencyclidine and Analogs	215	(2)
Lysergic Acid and Related Compounds	217	(2)
XXX-Methylfentanyl	219	(1)
Methaqualone and Mecloqualone	219	(1)
Benzodiazepines	220	(1)
Methadone	221	(1)
Analytical Approaches	222	(8)
Tandem MS	222	(2)
Chemical Derivatization for Enhancing Detection and Structure Elucidation	224	(2)
Generation of Favorable Derivatives to Improve the Limit of Detection	224	(1)
Generation of Favorable Mass Spectra through Derivatization	224	(2)
Generation of Ions More Suitable for Quantification	224	(1)
Generation of Ions Helpful for Structure Elucidation	224	(2)
Quantitative Analysis	226	(4)
Using an Isotope-Labeled Analog as an IS	226	(4)
Criteria for Selecting an Isotopic Analog as the IS	226	(1)
One-Point Calibration	227	(1)
Calibration Curve	227	(1)
Further Considerations	228	(2)
Instrumental Parameters	230	(1)
Chromatography--MS Applications	230	(6)
GC--MS	230	(2)
Operational Parameters	230	(2)
Precautions and Minimal Requirements for Using SIM Data as Qualitative Analysis Criteria	230	(1)
Precautions and Minimal Requirements for Using SIM Data for Quantitative Determination	231	(1)
Application of GC-MS Protocols in Drug Urinalysis: Targeted-Compound Identification	232	(1)
Liquid Chromatography-MS	232	(4)
References	236	(11)
SECTION IV DEVELOPING TECHNOLOGIES AND ANALYTICAL ISSUES	247	(51)
Chapter 10. Developing Analytical Technologies	247	(14)
Capillary Electrophoresis	247	(7)
Applications of CZE and MECC	248	(3)
Important Operational Parameters: pH, Buffer Additives, and Organic Modifiers	251	(2)
Development in Detection Technologies	253	(1)
Supercritical Fluid Extraction and Chromatography	254	(4)
Operational Parameters	255	(3)
Supercritical Fluid Chromatography	258	(1)
References	258	(3)
Chapter 11. Sample Differentiation	261	(22)
Physical Characterization of Tablets and Capsules	261	(1)
Impurity and Component Identification and Quantification	262	(5)
Amphetamines	262	(1)
Cocaine	263	(1)
Cannabis	264	(1)
Opiates	265	(2)
Analysis of Naturally Occurring Isotopes	267	(6)
Basic Methodology	267	(6)
Sample Preparation	267	(1)
Isotope-Ratio Determination	268	(1)
Applications	269	(4)
Intrinsic Sample Isotope-Ratio Variation as a Basis for Differentiation	269	(3)
Stable-Isotope Coding as a Tracing Mechanism: Methamphetamine Example	272	(1)
Analysis of Diastereoisomers and Enantiomers	273	(5)
NMR Spectrometry	273	(1)
Chromatographic Methods	274	(4)
GC Separation of Amphetamine and Methamphetamine Enantiomers	274	(1)
Chiral Column	274	(1)
Achiral Column	274	(1)
Liquid Chromatography	275	(3)
Mode of Separation	275	(2)
Applications	277	(1)
Conclusions	278	(1)
References	279	(4)
Chapter 12. Interpretation of Test Results	283	(15)
Sample Adulteration	283	(1)
In Vivo Adulteration	283	(1)
In Vitro Adulteration	283	(1)
Positive Results Derived From Nonabuse Exposure	284	(4)
Unintended Exposure	285	(2)
Marijuana	285	(1)
Cocaine	285	(2)
Others	287	(1)
Food and Licit Medication	287	(1)
Quantification	288
Concentration Near the Cutoff	289	(2)
Quantification Corrected with Creatinine Content and Urinary pH	289	(1)
Time Lapse Between Drug Exposure and Sample Collection	290	(1)
Stability	291
Identification and Quantification of Drug Metabolites	283	(11)
References	294	(4)
APPENDICES	298	(61)
Appendix I. Drug Classification and Other Pertinent Information	298	(15)
Appendix II. Metabolites of Common Drugs	313	(18)
Appendix III. Structural Frameworks for Drugs and Metabolite Listed in Appendices I and II	331	(12)
Appendix IV. Functional Groups That Complete the Structural Frameworks (Appendix III) for Drugs Listed in Appendices I and II	343	(16)
Index	359