Kassahun K, Farrell K, Zheng J J, Abbott F
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
J Chromatogr. 1990 May 18;527(2):327-41. doi: 10.1016/s0378-4347(00)82116-7.
A negative-ion chemical ionization gas chromatographic-mass spectrometric method for the determination of valproic acid (VPA) and fourteen of its metabolites in a single chromatographic run is reported. The assay features the use of four internal standards and is applicable to the analysis of small serum and urine volumes. A combination of pentafluorobenzyl and trimethylsilyl derivatization resulted in the [M - 181]- ion as the base peak for all the metabolites measured. When these ions were monitored sensitivities in the low picogram levels were achieved. The VPA metabolite profile was determined in pediatric patients on VPA monotherapy and on combined VPA therapy with either carbamazepine or clobazam. The recently characterized diene metabolite, (E,E)-2,3'-diene-VPA, was found to be a major serum metabolite of VPA. In the patient groups taking VPA in combination with carbamazepine, the induction of omega and omega-1 pathways of VPA metabolism was apparent, while the levels of the beta-oxidation products were significantly decreased.
报道了一种负离子化学电离气相色谱 - 质谱法，可在一次色谱运行中测定丙戊酸（VPA）及其十四种代谢物。该测定法采用四种内标，适用于少量血清和尿液的分析。五氟苄基和三甲基硅烷基衍生化的组合使得所测的所有代谢物的[M - 181]-离子成为基峰。当监测这些离子时，可实现低皮克水平的灵敏度。在接受VPA单一疗法以及VPA与卡马西平或氯巴占联合疗法的儿科患者中测定了VPA代谢物谱。最近鉴定出的二烯代谢物（E，E）-2,3'-二烯 - VPA被发现是VPA的主要血清代谢物。在接受VPA与卡马西平联合治疗的患者组中，VPA代谢的ω和ω-1途径的诱导明显，而β-氧化产物的水平显著降低。
