摘要
目的：建立人血浆中氯沙坦及其代谢物EXP3174同时测定的HPLC—MS方法，并研究健康受试者单剂量口服氯沙坦钾片后氯沙坦及其代谢物EXP3174的药代动力学特征。方法：血浆样品以乙腈沉淀蛋白后，进行HPLC—MS分析，色谱柱为Lichrospher C18流动相为甲醇-20mmol·L^-1醋酸铵水溶液（含0．1％的甲酸）（60：40，V／V），氯沙坦及其代谢物EXP3174的检测离子均为m／z207．1，传输区电压为250V。12名男性健康受试者口服100mg氯沙坦钾片后，测定血浆中氯沙坦及其代谢物EXP3174的浓度，计算主要药动学参数。结果：在1—2000ng·mL^-1范围内，氯沙坦及其代谢物EXP3174两者峰面积与内标峰面积的比值和浓度的线性关系均良好，批内、批间RSD均小于10％？受试者口服100mg氯沙坦钾片后，氯沙坦的血药浓度达峰时间为（1．6±1．1）h，达峰浓度为（890．2±476．4）ng·mL^-1,消除半衰期为（2．7±1．6）h；EXP3174的血药浓度达峰时间为（2．9±1．0）h，达峰浓度为（1233±611．6）ng·mL^-1，消除半衰期为（6．4±1．2）h。结论：本试验通过选择相同的碎片离子作为氯沙坦及其代谢物EXP3174的检测离子，提高了灵敏度和准确度；所建立的HPLC—MS分析方法准确、灵敏、方便，可用于氯沙坦及其代谢物的人体药动学研究.
Objective ：To establish an HPLC-MS method for the simultaneous determination of losartan and its metabolite EXP3174 in human plasma and their pharmacokinetics in Chinese healthy male volunteers. Methods： Plasma samples were deproteinized and separated by HPLC on a reversed phase C18 column with a mobile phase of methanol- ：20 mmol·L^-1 ammonium acetate water solution （containing 0. 1% formic acid） （60： 40, V/V）. HPLC-MS was performed in the selected ion monitoring （SIM） mode using target ions at m/z 207. 1 for both losartan and EXP3174. The fragment voltage was 250 V. A single oral dose of 100 mg losartan potassium tablet was administered to 12 healthy Chinese male volunteers, then the plasma concentrations of losartan and EXP3174 were detected by HPLC-MS and their pharmacokinetic parameters were evaluated. Results： Calibration curves for both losartan and EXP3174 were linear over the range of 1 -2 000 ng·mL^-1. The RSD of intra-run and inter-run were both less than 10%. For losartan, the pharmacokinetic parameter t C and t1/2 were （ 1.6± 1.1 ） h, （890. 2± 476.4） ng·mL^-1 and （2.7±1.6） h, respectively. For EXP3174, the pharmacokinetic parameter t C and t1/2 were （2. 9 ± 1.0） h, （1 233 ±611.6）ng·mL^-1 and （6. 4 ± 1.2） h, respectively. Conclusion ： In this experiment, the same fragment ion m/z 207. 1 was selected as the target ion for both losartan and EXP3174, which improved the sensitivity and accuracy of the assay for the two analytes. The assay was proved to be sensitive, accurate and convenient. It can be applied to the pharmacokinetics study of losartan and EXP3174 in humans.
出处
《药学与临床研究》
2009年第2期115-119,共5页
Pharmaceutical and Clinical Research
