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本文报道了乙吗噻嗪血药浓度测定的一种高效液相色谱测定法,和六例正常成人口服300mg与静脉注射100mg乙吗噻嗪的药代动力学有关参数。本测定法以甲醇、水、四甲基乙二胺及冰乙酸组成流动相,固定相为ODS(10μm),紫外检测器波长为254nm,并以氯氮平为内标物。血浆中最低有效检测浓度为0.05μg/ml,平均回收率为97.7%,不同浓度水平测定结果的日内和日间变异系数均小于10%。口服和静脉注射的药代动力学参数分别按开放式一室模型和二室模型求算。两种给药方式的消除半衰期(t_(1/2β))分别为2.23±0.61h和2.39±1.43h,表观分布容积(Vd)为2.08±1.22L·Kg~(-1)和3.10±1.36L·Kg~(-1),血浆清除率(Cl_p)为0.66±0.40L·Kg~(-1)·h~(-1)和0.68±0.42L·Kg~(-1)·h~(-1),均无显著性差异(P>0.05)。口服吸收速率常数(Ka)为2.139±1.068h~(-1),血药浓度达峰时间(Tmax)为1.5±0.55h,表明吸收迅速良好。生物利用度F值在不同个体差异较大,平均为45±30%。
In this paper, a high performance liquid chromatography (HPLC) assay was developed for the determination of ethnothiazine in plasma and pharmacokinetic parameters of six 300 mg oral and 100 mg ethmozine orally administered to normal adults. The mobile phase consisted of methanol, water, tetramethylethylenediamine and glacial acetic acid. The stationary phase was ODS (10μm). The wavelength of UV detector was 254nm. Clozapine was used as internal standard. The lowest detectable concentration in plasma was 0.05 μg / ml with an average recovery of 97.7%. The intra-and inter-day coefficients of variation for different concentrations were less than 10%. Pharmacokinetic parameters of oral and intravenous injection were calculated according to the open one-compartment model and two-compartment model respectively. The elimination half-lives (t 1 / 2β) of the two administration modes were 2.23 ± 0.61h and 2.39 ± 1.43h, respectively. The apparent volume of distribution (Vd) was 2.08 ± 1.22L · Kg -1 and 3.10 ± 1.36L · Kg -1, and the plasma clearance (Cl_p) was 0.66 ± 0.40L · Kg -1 · h -1 and 0.68 ± 0.42L · Kg -1 · h -1, (-1), no significant difference (P> 0.05). The oral absorption rate constant (Ka) was 2.139 ± 1.068 h -1, and the peak plasma concentration (Tmax) was 1.5 ± 0.55 h, indicating that the absorption was rapid and good. Bioavailability F value in different individuals larger, with an average of 45 ± 30%.