tailieunhanh - Drugs and Poisons in Humans - A Handbook of Practical Analysis (Part 31)

Introduction: Bromisovalum (α-bromoisovalerylurea, bromovalerylurea, Brovarin) ( Figure ) has long been being used as a hypnotics or sedative since many years ago. It is not only prescribed as an ethical drug, but also contained in some analgesic- antipyretics and hypnotics being sold as over-the-counter drugs. Because of the easiness of getting it, bromisovalum is one of the most important drugs in poisoning in Japan. The analysis of bromisovalum is being made by GC [1, 2], GC/MS [3], HPLC [4, 5] and LC/MS [6–8]. Because of its thermolability, HPLC or LC/MS is more recommendable than GC or GC/MS to obtain. | Bromisovalum by Keiko Kudo and Noriaki Ikeda Introduction Bromisovalum a-bromoisovalerylurea bromovalerylurea Brovarin Figure has long been being used as a hypnotics or sedative since many years ago. It is not only prescribed as an ethical drug but also contained in some analgesic- antipyretics and hypnotics being sold as over-the-counter drugs. Because of the easiness of getting it bromisovalum is one of the most important drugs in poisoning in Japan. The analysis of bromisovalum is being made by GC 1 2 GC MS 3 HPLC 4 5 and LC MS 6-8 . Because of its thermolability HPLC or LC MS is more recommendable than GC or GC MS to obtain good reproducibility. In this chapter three kinds of methods for extraction of bromisovalum from blood and urine and its HPLC analysis are presented. Reagents and their preparation Bromisovalum Nippon Shinyaku Co. Ltd. Kyoto Japan Wako Pure Chemical Industries Ltd. Osaka Japan and other manufacturers is dissolved in methanol to prepare 1 mg mL standard solution. Phenytoin internal standard ISa Wako Pure Chemical Industries and other manufacturers is dissolved in methanol to prepare 1 mg mL standard solution. HPLC conditions Column a reversed-phase column CAPCELL-PAK C18 MG b 250 x 3 mm i. d. particle diameter 5 pm Shiseido Tokyo Japan mobile phase acetonitrile 8 mM KH2PO4 solution 35 65 v v c detection wavelength 210 nm flow rate mL min column temperature 40 C. O Figure Br CH2 CHCH2 CTh I CH3 CHCHCONHCONTh CHCHCONHCONTh CTh CTh bromisovalum apronalide Bromisovalum and its related compounds. Br CH3CH2CH2CH2CHCONHCONH2 2 - bromohexanoylurea Springer-Verlag Berlin Heidelberg 2005 294 Bromisovalum Procedures i. Extraction with an Extrelut column 9 i. A 1-mh or g aliquot of a specimen whole blood serum or urine is mixed with 5 ph phenytoin solution IS 1 mg mh and 1 mh of M hydrochloric acid solution d in a centrifuge tube. ii. The mixture is vortex-mixed for 10 s. iii. It is centrifuged 4 C 2 500 rpm 15 min to obtain a