作者：胡岚岚, 汤建林, 徐颖, 周世文, 邹欢

作者单位：第三军医大学新桥医院临床药理基地, 重庆 400037

关键词：盐酸沙格雷酯;UPLC-MS/MS;药代动力学;血浆

摘要：

建立一种快速、准确测定人血浆中盐酸沙格雷酯的UPLC-MS/MS分析方法。以阿立哌唑为内标,0.2 mL含药血浆经乙腈沉淀蛋白后进样分析;流动相组成为乙腈:0.01 mol/L甲酸铵水溶液=30:70,梯度洗脱方式,乙腈比例在2 min内从30%变为65%,流量0.3 mL/min,柱温为35 ℃,进样量3 L。质谱条件:气动辅助电喷雾离子化(ESI)源;正离子检测(MRM)模式,盐酸沙格雷酯质荷比为(m/z 430.1m/z 135.1)和内标阿立哌唑质荷比为(m/z 448.1m/z 285.1)。结果表明:盐酸沙格雷酯在10.0~1 280.0 ng/mL范围内呈线性,定量限为10.0 ng/mL,基质效应影响小,日内、日间变异系数均小于13.3%,相对回收率在92.0%~118.2%之间。该方法准确、快速、灵敏,可用于微量血浆的盐酸沙格雷酯血药浓度测定、人体内药代动力学及生物等效性研究。

Quantification of sarpogrelate hydrochloride in human plasma by UPLC-MS/MS and its application in a pharmacokinetic study

HU Lanlan, TANG Jianlin, XU Ying, ZHOU Shiwen, ZOU Huan

Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China

Abstract: To establish a rapid and accurate method using UPLC-MS/MS for quantification of sarpogrelate hydrochloride in human plasma. One-step protein precipitation with acetonitrile was used to extract the analytes from the plasma. Sarpogrelate and aripiprazole (internal standard, I.S.) were separated on a reversed-phase C18 column within 3.5min, using acetonitrile: ammonium formate (0.01 mol/L) (30:70, ν/ν) as mobile phase at a flow rate of 0.3 mL/min. Mass spectrometry: The analytes were detected by the electronic-spryionization(ESI), Selected multiple reaction monitoring (MRM) using the precursor to product ion combinations of m/z 430.1→135.1 and m/z 448.1→285.1 was performed to detected sarpogrelate hydrochloride and the I.S., respectively. The method was linear over the concentration range of 10.0-1 280.0 ng/mL. The lower limit of quantification was 10 ng/mL. Intra-day inaccuracy was within 13.3% and inter-day was less than 12.2%. Matrix effects were minor, the recovery of the method was between 92.0% and 118.2%. The validated method was developed for quantification of sarpogrelate hydrochloride in small volumes of plasma. The method was successfully applied to a pharmacokinetics and bioavailability of sarpogrelate hydrochloride.

Keywords: sarpogrelate hydrochloride;UPLC-MS/MS;pharmacokinetics;plasma

2015, 41(7): 55-59  收稿日期: 2015-1-12;收到修改稿日期: 2015-3-9

基金项目: 

作者简介: 胡岚岚(1984-),女,安徽安庆市人,硕士研究生,专业方向为药物分析。

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