Gomez L E, Lehmann P A
Departamento de Farmacología y Toxicología, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, Mexico City, Mexico.
J Chromatogr. 1992 Mar 27;575(2):306-10. doi: 10.1016/0378-4347(92)80162-j.
A sensitive gas chromatographic method with flame ionization detection was developed for the analysis in plasma of the novel anticonvulsant D,L-3-hydroxy-3-ethyl-3-phenylpropionamide (HEPP), using D,L-2-hydroxy-2-ethyl-2-phenylacetamide as the internal standard. HEPP was extracted from alkalinized plasma into dichloromethane and quantified after derivatization with bis(trimethylsilyl)-trifluoroacetamide: Standard curves were linear from 0.5 to 50 and from 2 to 100 micrograms/ml of plasma, using 1.5 and 5 micrograms of the internal standard, respectively. The lower limit of detection at a signal-to-noise ratio of 3 standard deviations was 0.33 micrograms/ml of sample. The sensitivity, accuracy and reproducibility of the method were shown to be satisfactory for pharmacokinetic studies of HEPP. After intraperitoneal administration of 50 mg/kg to Wistar rats, the principal kinetic parameters were: absorption half-life = 0.04 h; volume of distribution = 1.32 l/kg; clearance = 4.40 ml/min; peak concentration = 50 micrograms/ml; peak time = 0.25 h; mean residence time = 4.55 h.
建立了一种采用火焰离子化检测的灵敏气相色谱法，以D,L-2-羟基-2-乙基-2-苯基乙酰胺为内标，用于分析新型抗惊厥药D,L-3-羟基-3-乙基-3-苯基丙酰胺（HEPP）在血浆中的含量。HEPP从碱化血浆中萃取至二氯甲烷中，并用双（三甲基硅基）-三氟乙酰胺进行衍生化后定量：分别使用1.5微克和5微克内标时，标准曲线在血浆浓度为0.5至50微克/毫升以及2至100微克/毫升范围内呈线性。在信噪比为3倍标准差时，检测下限为0.33微克/毫升样品。该方法的灵敏度、准确度和重现性对于HEPP的药代动力学研究而言令人满意。给Wistar大鼠腹腔注射50毫克/千克后，主要动力学参数为：吸收半衰期=0.04小时；分布容积=1.32升/千克；清除率=4.40毫升/分钟；峰浓度=50微克/毫升；达峰时间=0.25小时；平均驻留时间=4.55小时。
