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目的:建立测定人血浆中依普利酮浓度的LC-MS/MS方法,并应用于依普利酮片在中国健康人体内的药动学研究。方法:血浆采用EDTANa_2作为稳定剂,并用预冰水浴冷却乙腈沉淀蛋白处理样品;以0.05%甲酸0.1%醋酸铵溶液-0.05%甲酸甲醇溶液为流动相,线性梯度洗脱,采用Wondasil-C_(18)色谱柱(4.6 mm×150 mm,5μm)进行分离;多反应离子监测[M+H]~+离子通道分别为m/z 415.2→m/z 163.1(依普利酮)、m/z 433.2→m/z 337.4(依普利酮酸)和m/z 393.1→m/z 355.1(内标地塞米松)。结果:建立的LC-MS/MS法测定血浆中依普利酮质量浓度在10.00~2 500 ng·mL~(-1)范围内线性关系良好,最低定量限为10.00 ng·mL~(-1),经方法验证符合生物样本分析的要求。12名受试者单次给药25、50、100 mg依普利酮后,C_(max)分别为(505.7±133.1)、(946.6±226.3)、(1 847±433)ng·mL~(-1),T_(max)分别为(1.3±0.5)、(1.3±0.8)、(1.6±0.8)h,t_(1/2)分别为(2.8±0.8)、(2.9±0.8)、(3.3±0.7)h,AUC_(0-24)分别为(2 310±728)、(4 889±1 808)、(9 691±2 733)ng·h·mL~(-1),AUC_(0-∞)分别为(2 395±749)、(5 051±1 789)、(9 788±2 751)ng·h·mL~(-1)。结论:建立的血浆中依普利酮LC-MS/MS测定法可用于依普利酮的临床药动学研究。
OBJECTIVE: To establish a LC-MS / MS method for the determination of eplerenone in human plasma and to study the pharmacokinetics of eplerenone tablet in Chinese healthy volunteers. METHODS: EDTANa_2 was used as a stabilizer in plasma and acetonitrile-precipitated protein was treated with a pre-ice water bath. The sample was eluted with a linear gradient of 0.05% formic acid 0.1% ammonium acetate-0.05% formic acid in methanol. ) Column (4.6 mm × 150 mm, 5 μm). M + H] + ion channels were m / z 415.2 → m / z 163.1 (eplerenone), m / z 433.2 → m / z 337.4 (eplerenone) and m / z 393.1 → m / z 355.1 (internal standard dexamethasone). Results: The established LC-MS / MS method showed a good linear relationship between the concentration of eplerenone and plasma in the range of 10.00-2 500 ng · mL -1. The lowest limit of quantification was 10.00 ng · mL -1 ), The method validation in line with the requirements of biological sample analysis. After the single administration of 25, 50 and 100 mg eplerenone, the Cmax of 12 subjects were (505.7 ± 133.1), (946.6 ± 226.3) and (8447 ± 433) ng · mL ~ ( -1, and T max were (1.3 ± 0.5), (1.3 ± 0.8), (1.6 ± 0.8) h and (t 1/2) were respectively (2.8 ± 0.8) and 3.3 ± 0.7) h and AUC_ (0-24) were respectively (2 310 ± 728), (4 889 ± 1 808) and (9 691 ± 2733) ng · h · mL -1 -∞) were (2 395 ± 749), (5 051 ± 1 789) and (9 788 ± 2 751) ng · h · mL -1, respectively. CONCLUSION: The established eplerenone LC-MS / MS assay in plasma can be used for the clinical pharmacokinetics of eplerenone.