摘要
A simple and sensitive high-performance liquid chromatography mass spectrometry（LC-MS）method for the simultaneous determination of irbesartan and hydrochlorothiazide in human plasma was developed and applied to a pharmacokinetic study. Acetaminophen was used as the internal standard（IS）.Sample pretreatment using liquid-liquid extraction with ethyl acetate was used.The analysis was carried out on an Elite SinoChrom ODS-BP C_（18）column with a mobile phase composed of acetonitrile-water （35：65,v/v）.Target ions were [M-H]^-m/z 427.25 for irbesartan,[M-H]^-m/z 295.95 for hydrochlorothiazide and [M-H]^- m/z 150.05 for the IS via an electrospray ionization（ESI）source.The intra-and inter-day precision（RSD%）was below 14.5% for irbesartan and hydrochlorothiazide,and the accuracy（RE%）was less than 1.9% and-2.0% for irbesartan and hydrochlorothiazide,respectively.The linear calibration curves were obtained in the concentration range of 10-5000 ng/mL （r0.99）for irbesartan and 1-200 ng/mL（r0.99）for hydrochlorothiazide with the lower limit of quantification（LLOQ）of 10 ng/mL and 1 ng/mL,respectively.The method was applied to a clinical pharmacokinetic study of a tablet containing irbesartan and hydrochlorothiazide in healthy Chinese volunteers after oral administration.
建立了适用于测定人血浆中厄贝沙坦和氢氯噻嗪浓度的液相色谱-质谱(LC-MS)法,并将其应用于厄贝沙坦氢氯噻嗪人体药代动力学研究。人血浆样品采用液-液萃取法提取,内标为对乙酰氨基酚。采用依利特C_(18)柱,以乙腈-水(35:65,v/v)为流动相,选择离子监测负离子模式检测,厄贝沙坦m/z为427.25,氢氯噻嗪m/z为295.95,内标对乙酰氨基酚m/z为150.05。厄贝沙坦和氢氯噻嗪的日内和日间精密度(RSD%)均低于14.5%,准确度(RE%)分别低于1.9%和-2.0%。厄贝沙坦在10-5000ng/mL浓度范围内线性关系良好(r>0.99),氢氯噻嗪在1-200ng/mL浓度范围内线性关系良好(r>0.99)。所建立的方法已成功应用于厄贝沙坦氢氯噻嗪人体药代动力学研究。
