Benzodiazepines A Handbook. Basic Data, Analytical Methods, Pharmacokinetics and Comprehensive Literature

To comment at length on the importance of the benzodiazepines seems superfluous within the scope of this preface. No other class of active substances has experienced an even approximately compa­ rable advance in the past two decades. It is therefore not surprising that the formerly dominant barbiturates and bromocarbamides have had to give way in many fields to the benzodiazepines, which now rank first (Proudfoot and Park [1828]). Closely linked with the great therapeutic importance of the benzodia­ zepines are analytical problems. Detection and the determination of blood levels can be necessary under therapeutic aspects, for instance in working out optimally effective levels in the treatment of epileptic conditions ("drug monitoring"), but also in connection with questions at issue in toxicology and traffic medicine. A toxicological analysis can be subdivided into the following steps: Detection (identification including screening) Determination (e. g. blood, plasma or serum levels) Interpretation of the analytical results. This book is intended as a contribution to each of these chapters: The part "Analytical Data" (pp.I-122) gives a comprehensive collec­ tion of data, e.g. general and chromatographic data (TLC, GLC) as well as spectra (UV, IR, MS) of 19 commercial preparations, 23 important metabolites and 18 hydrolysis derivatives. Information about biotransformation and the possible formation of aminobenzo­ phenone derivatives is also given. The most important analytical methods are presented in an extensive review on pp.123-204 in order to make it possible to select the optimum method on the basis of the essential data.

Formula Index and Melting Points.- Biotransformation.- Index of Treated Substances.- Formation of Aminobenzophenones and Other Hydrolysis Products (Survey).- Formation of the Hydrolysis Derivatives (Formula Index).- Some Important Data (Molecular Weight, Molecular Formula, Mass-Spectrum Peaks).- TLC-Data.- Technical Conditions.- Data (Rf-Values and Detection).- GLC-Data.- Technical Conditions.- Data (Retention Times and Retention Index, SE-30 and OV-17).- Infrared- and Mass-Spectra.- Ultraviolet-Spectra.- Table of Absorption Maxima.- Spectra.- Presentation of Analytical Methods.- Methods for the Detection and Determination of Various Benzodiazepines (Simultaneous-Methods).- Methods for the Detection and Determination of a Special Benzodiazepine (Mono-Methods).- Chlordiazepoxide.- Diazepam (see also p. 187).- Oxazepam.- Nitrazepam.- Medazepam.- Clorazepate.- Lorazepam (see also p. 167).- Prazepam.- Clonazepam (see also p. 155, 170, 171).- Flurazepam.- Bromazepam(see also p. 199).- Flunitrazepam (see also p. 171).- Clobazam.- Camazepam.- Blood-, Serum- and Plasma-Levels and Other Pharmacokinetic Data from Literature.- Chlordiazepoxide.- Diazepam.- Other Pharmacokinetic Data.- Oxazepam.- Nitrazepam.- Medazepam.- Clorazepate.- Lorazepam.- Prazepam.- Clonazepam.- Flurazepam.- Bromazepam.- Flunitrazepam.- Clobazam.- Camazepam.- Ketazolam.- Triazolam.- Lormetazepam.- Ranges of Maximum Concentrations After Oral Administration.- Chlordiazepoxide.- Diazepam (single dose).- Oxazepam (single dose).- Nitrazepam (single dose).- Medazepam (single dose).- Lorazepam (single dose).- Bromazepam (single dose).- Diazepam (multiple dose).- Nordiazepam (after multiple doses of Diazepam).- Survey of Benzodiazepine Literature.- Absorption.- Benzodiazepines in Relation to Mother and Child.- Bioavailability Studies.- Biotransformation/Metabolism.- Disposition.- Effects and Interactions with Other Compounds.- Emergency-Drug-Analysis.- Extraction from Biological Samples (Selection).- Fluorescence/Fluorometry.- Gas-Liquid-Chromatography.- General Analytical Data.- General Treatment.- High-Pressure-Liquid-Chromatography.- Hydrolysis of Benzodiazepines.- Infrared-Spectra.- Levels (Blood, Plasma, Serum).- Mass-Spectra.- NMR-Spectra.- Pharmacokinetics.- Pharmacology and Clinical Investigations.- Poisoning (Treatment, Reports, Cases).- Polarography.- Protein-Binding.- Radioactive-Labelled-Benzodiazepines.- Radioimmunoassay and Other Immunoassays.- Screening.- Side-, Adverse-, Residual- and Withdrawal-Effects.- Sleep-Effects.- Synthesis.- Theory of Action/The Benzodiazepine Receptor.- Thin-Layer-Chromatography.- Toxicity/Toxicology.- Traffic-Medicine.- UV-and VIS-Spectroscopy.- Other Themes.- References.- Alphabetical List 1.- Alphabetical List 2.- Alphabetical List 3.- Addendum 1.- Alphabetical List 4.- Addendum 2.- Screening of Benzodiazepines in Urine (inside backcover).