LC-MS/MS法测定人血浆中盐酸洛哌丁胺

Determination of loperamide hydrochloride in human plasma using LC-MS/MS

目的建立人血浆中盐酸洛哌丁胺的液相色谱-质谱联用测定法（LC-MS／MS）。方法血浆样品中盐酸洛哌丁胺与盐酸小檗碱（内标）经甲醇液．液提取后，采用ZORBAXSB—C18色谱柱（2．1mm×150mm×5μm），柱温35℃，流动相为乙腈：0．1％甲酸（60：40，V／V），流速为0．4mL／min，进样量10μL。电喷雾离子源（ESI），正离子检测，以多反应监测（MRM）方式进行定量分析，用于监测的离子为m／z477→266（盐酸洛哌丁胺）和m／z366→292（内标）。结果盐酸洛哌丁胺的检测下限为0．2ng／mL（S／N=3），在浓度0．5～500ng／mL范围内线性良好（r=0．9982），低、中、高浓度（1ng／mL、20ng／mL、400ng／mL）的平均回收率分别为84．6％，88．5％和90．2％，日内与日问RSD分别小于6％与7％。结论LC—MS／MS法可用于盐酸洛哌丁胺的定性定量分析。

Objective A LC-MS/MS method for analysis of loperamide hydrochloride in human plasma was developed. Methods Loperamide hydrochloride and berberine hydrochloride （internal standard） were separated from human plasma samples by liquid-liquid extraction with methanol. Chromatographic separation was performed on a ZORBAX SB-C18 （2. 1mm ×150mm× 5μm） column at 35℃. Acetonitrile/0. 1% formic acid （60：40 by volume） was used as mobile phase at a flow rate of 0.4mL/min, and the injection volume was 10μL. Electrospray ionization（ESI） source was applied and operated in positive ion mode. Quantification was performed using multiple reaction monitoring（MRM） of the transitions m/z 477→266 and m/z 366→292 for loperamide hydrochloride and the internal standard, respectively. Results The limit of detection of loperamide hydrochloride was 0.2ng/mL （ S/N = 3 ）, and the calibration curve in the concentration range of 0.5 - 500ng/mL showed a good linear （r = 0. 9982）. The average recoveries of low, medium and high concentrations（lng/mL, 20ng/mL, 400ng/mL） were 84.6%, 88.5% and 90.2%, respectively. The precisions （RSD） of winth-day and between-day were less than 6% and 7%, respectively. Conclusion This LC-MS/MS method can be used for qualitative and quantitative analysis of loperamide hydroehloride.