Darius J, Meyer F P
Department of Clinical Pharmacology, University Hospital, Otto von Guericke University, Magdeburg, Germany.
J Chromatogr B Biomed Appl. 1994 Jun 17;656(2):343-51. doi: 10.1016/0378-4347(94)00129-4.
A sensitive capillary gas chromatographic-mass spectrometric method for the determination of valproic acid and 7 of its metabolites is described. It is based on the selected-ion monitoring of the tert.-butyldimethylsilyl derivatives using N-(tert.-butyldimethylsilyl)-N-methyl-trifluoracetamid (MTBSTFA) as the derivatization reagent. The limits of detection for valproic acid and its metabolites are in the low ng/ml-range, except for the 4-hydroxy metabolite with a limit of detection of 100 ng/ml. The method has been tested against an established GC method for valproic acid. The assay has been used for therapeutic drug monitoring in epileptic pediatric patients. The concentrations of the omega- and omega 1-oxidation metabolites in a group of patients receiving additional antiepileptic drugs were found to be significantly enhanced compared to the levels found in a monotherapy group.
描述了一种用于测定丙戊酸及其7种代谢物的灵敏毛细管气相色谱-质谱法。该方法基于使用N-(叔丁基二甲基硅烷基)-N-甲基三氟乙酰胺(MTBSTFA)作为衍生化试剂对叔丁基二甲基硅烷基衍生物进行选择离子监测。丙戊酸及其代谢物的检测限在低纳克/毫升范围内，但4-羟基代谢物的检测限为100纳克/毫升。该方法已与一种既定的丙戊酸气相色谱法进行了对比测试。该测定法已用于癫痫儿科患者的治疗药物监测。与单药治疗组相比，发现一组接受额外抗癫痫药物治疗的患者中ω-和ω1-氧化代谢物的浓度显著升高。
