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Drugs and Poisons in Humans - A Handbook of Practical Analysis (Part 30)

Introduction: Benzodiazepines show antianxiety, hypnotic, anticonvulsant and muscle-relaxant effects. This group of drugs has wide safety dose ranges; it means that the ratio of the LD50 to the ED50 (therapeutic index) is high. Because of its safety, benzodiazepines are being widely used in the world. Some of benzodiazepines are also being abused or used for so-called “drug facilitated sexual assault”, and thus they are under the control of the Narcotics and Psychotropics Control Law; in Japan, triazolam abuse has become one of the serious social problems. In this chapter, a GC/MS method for simultaneous analysis of 22 kinds of benzodiazepines. | 3.4 II.3.4 Benzodiazepines by Hiroshi Seno and Hideki Hattori Introduction Benzodiazepines show antianxiety hypnotic anticonvulsant and muscle-relaxant effects. This group of drugs has wide safety dose ranges it means that the ratio of the LD50 to the ED50 therapeutic index is high. Because of its safety benzodiazepines are being widely used in the world. Some of benzodiazepines are also being abused or used for so-called drug facilitated sexual assault and thus they are under the control of the Narcotics and Psychotropics Control Law in Japan triazolam abuse has become one of the serious social problems. In this chapter a GC MS method for simultaneous analysis of 22 kinds of benzodiazepines listed in Table 4.1 is described. In addition the LC MS analysis of triazolam and its metabolites 4-hydroxy-triazolam and a-hydroxytriazolam is also presented. GC MS analysis of benzodiazepines in blood and urine Reagents and their preparation The pure powder of the 22 kinds of benzodiazepines was donated by each pharmaceutical manufacturers according to the authors request a some of benzodiazepines now obtainable from Sigma St. Louis MO USA . 1 M Sodium bicarbonate solution a 8.4-g aliquot of sodium bicarbonate is dissolved in distilled water to prepare 100 mL solution. 2 M Sodium acetate solution a 27.5-g aliquot of sodium acetate is dissolved in distilled water to prepare 100 mL solution. GC MS conditions Column a DB-5 fused silica capillary column 30 m x 0.25 mm i.d. film thickness 0.25 pm J W Scientific Folsom CA USA . GC conditions instrument a GC-17A gas chromatograph Shimadzu Corp. Kyoto Japan column oven temperature 150 C 1 min 20 C min 300 C 6.5 min injection temperature 250 C carrier gas He its flow rate 0.9 mL min sample injection splitless mode for 1 min followed by the split mode. MS conditions a QP-5050A mass spectrometer Shimadzu Corp. ionization EI electron energy 70 eV interface temperature 250 C. Springer-Verlag Berlin Heidelberg 2005 284 Benzodiazepines o .