论文部分内容阅读
目的:建立一种快速测定人血浆中美托拉宗浓度的液相色谱-串联质谱色谱法,用以研究美托拉宗在健康人体内的药动学。方法:色谱柱:TC-C_(18)(150 mm×4.6mm,5μm),流动相:甲醇:去离子水(70:30),质谱离子源为电喷雾离子化(ESI)源,选择性离子检测方式检测;血浆样品在0.05～100 ng·ml~(-1)内线性关系良好,定量下限为0.05 ng·ml~(-1),精密度和准确度试验均符合生物分析要求。健康受试者口服3个单剂量(0.5,1,2 mg)进行药物动力学研究,采用DAS2.0软件计算药动学参数。结果:服用0.5,1,2 mg美托拉宗后的药动学参数,t_(1/2)分别为(8.6±2.6)、(7.0±1.2)、(7.6±1.9)h;t_(max)分别为(1.7±0.9)、(1.6±0.6)、(1.5±1.3)h;C_(max)分别为(9.3±1.9)、(18.4±3.6)、(36.8±7.1)ng·ml~(-1);AUC_(0～48)分别为(52.17±14.00)、(96.51±19.15)、(162.4±26.9)ng·h·ml~(-1);呈线性动力学特征。结论:该方法灵敏度高、专属性强、准确、简便,适用于美托拉宗的人体药动学研究。
OBJECTIVE: To establish a liquid chromatography-tandem mass spectrometry (LC-MS / MS) method for the rapid determination of the concentration of medetamizon in human plasma and to study the pharmacokinetics of metrazole in healthy volunteers. METHODS: The chromatographic column was electrospray ionization (ESI) with TC-C 18 (150 mm × 4.6 mm, 5 μm) and methanol: deionized water (70:30) The linearity of the plasma samples was within 0.05-100 ng · ml -1. The lower limit of quantitation was 0.05 ng · ml -1. The precision and accuracy of the assay were in accordance with the requirements of bioanalysis. Healthy subjects were orally administered with 3 single doses (0.5, 1, 2 mg) for pharmacokinetic studies and pharmacokinetic parameters were calculated using the DAS 2.0 software. Results: The pharmacokinetic parameters (t 1/2) were (8.6 ± 2.6), (7.0 ± 1.2) and (7.6 ± 1.9) h respectively after taking 0.5, 1, ) Were (1.7 ± 0.9), (1.6 ± 0.6) and (1.5 ± 1.3) h respectively, and the values of C max were (9.3 ± 1.9), (18.4 ± 3.6) and (36.8 ± 7.1) ng · ml ~ -1). The AUC_ (0 ~ 48) values were (52.17 ± 14.00), (96.51 ± 19.15) and (162.4 ± 26.9) ng · h · ml -1, respectively. Conclusion: This method has high sensitivity, specificity, accuracy and convenience. It is suitable for human pharmacokinetics study of metolazone.