tailieunhanh - Drugs and Poisons in Humans - A Handbook of Practical Analysis (Part 37)

Introduction: As antiepileptics, phenytoin, mephenytoin, nirvanol and ethotoin are being used for treatments of grand mal and complex partial seizures. A iminostilbene derivative carbamazepine, phenobarbital (one of the barbiturates) and some benzodiazepines are also being well used as antiepileptics ( Figure ). Poisoning cases due to accidental and suicidal ingestion of these antiepileptics were reported [1]. For analysis of antiepileptics, methods using HPLC [2–15], LC/MS [16], GC [17, 18] and GC/MS [19,20] were reported. Among them, HPLC methods are being used most commonly. In this chapter, two HPLC methods, dealing with analysis of phenytoin and other antiepileptics together with. | Antiepileptics by Einosuke Tanaka Introduction As antiepileptics phenytoin mephenytoin nirvanol and ethotoin are being used for treatments of grand mal and complex partial seizures. A iminostilbene derivative carbamazepine phenobarbital one of the barbiturates and some benzodiazepines are also being well used as antiepileptics Figure . Poisoning cases due to accidental and suicidal ingestion of these antiepileptics were reported 1 . For analysis of antiepileptics methods using HPLC 2-15 LC MS 16 GC 17 18 and GC MS 19 20 were reported. Among them HPLC methods are being used most commonly. In this chapter two HPLC methods dealing with analysis of phenytoin and other antiepileptics together with their metabolites in serum 11 and plasma 15 are presented. O Figure 1 ethosuximide 6 oxazepam 2 primidone GHs CIL CO V CHs CO NH 3 phenobarbital 7 nitrazepam 5 phenytoin 4 carbamazepine 8 diazepam Structures of antiepileptics and their analogs. Springer-Verlag Berlin Heidelberg 2005 352 Antiepileptics HPLC analysis of antiepileptics in serum 11 Reagents and their preparation Carbamazepine ethosuximide phenytoin primidone phenobarbital diazepam oxazepam nitrazepam and 5- 4-methylphenyl -5-phenylhydantoin internal standard IS can be all purchased from Sigma St. Louis MO USA . Each of above drugs is dissolved in methanol to prepare 1 mg mL solution. By diluting the 1 mg mL solution with methanol solutions at various concentrations in the range of pg mL are prepared for drugs to be quantitated because they are used for constructing each calibration curve. HPLC conditions Column a reversed phase column TSK gel super-ODS 100 x mm i. d. particle diameter 2 pm Tohso Tokyo Japan . Mobile phase acetonitrile 8 mM phosphoric acid aqueous solution 3 7 v v its flow rate mL min detection wavelength 215 nm column oven temperature room temperature. Procedure i. A volume of serumb 100 pL of M hydrochloric acid solution 50 pL of IS solution and 3 mL .