A Validated Ultra-Performance Liquid Chromatography Tandem Triple Quadrupole Mass Spectrometric Method for Fast Determination of Losartan in Rabbit Plasma
A Validated Ultra-Performance Liquid Chromatography Tandem Triple Quadrupole Mass Spectrometric Method for Fast Determination of Losartan in Rabbit Plasma
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DOI：
10.1093/chromsci/bmy114
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发表时间：
2019-04-01
影响因子：
1.3
通讯作者：
Al-Jenoobi, Fahad Ibrahim
中科院分区：
文献类型：
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作者：
Alam, Mohd Aftab;Abou Obaid, Nuha Ibrahim;Al-Jenoobi, Fahad Ibrahim
建立了超高效液相色谱-串联质谱法（UPLC-MS-MS）测定兔血浆中氯沙坦浓度的方法。以多反应监测模式监测洛沙坦和依普罗沙坦（IS）的质子化加合物。氯沙坦和依普罗沙坦的分子量分别为m/z 423.19 > 207和m/z 423.19 > 180;依普罗沙坦的分子量分别为m/z 425.11 > 135和m/z 425.11 > 107。采用蛋白沉淀法提取血浆中的氯沙坦。以梯度模式使用包含水（0.1%甲酸）（A）和乙腈（0.1%甲酸）（B）的移动的相。在Acquity（UPLCBEH）-B-（R）C18 1.7 m，2.1 x 50 mm柱上洗脱分析物。样品运行时间为3.0 min。验证参数：准确度、精密度和回收率均在推荐限度内。在实验室稳定性研究以及制备后稳定性研究中，氯沙坦以及内标物保持稳定。测定氯沙坦的Cmax（182.79 ± 23.80 ng/mL）、Tmax（1.16 ± 0.28 h）、AUC 0-t（1188.57 ± 404.60 ng h/mL）和Kel（0.0954 ± 0.0140 h（-1））等药代动力学参数。方法可用于家兔体内氯沙坦的药代动力学研究，也可用于其他动物血浆样品中氯沙坦的测定。
A rapid UPLC-MS-MS method was developed and validated for determination of losartan in rabbit plasma. Protonated adducts of losartan and eprosartan (IS) were monitored in multiple reaction monitoring mode. Molecular masses of daughter species of losartan were m/z 423.19 > 207 and m/z 423.19 > 180; and of eprosartan were m/z 425.11 > 135 and m/z 425.11 > 107. Losartan from plasma samples was extracted by protein precipitation method. The mobile phase comprising water (0.1% formic acid) (A) and acetonitrile (0.1% formic acid) (B) was used in gradient mode. Analytes were eluted on Acquity (UPLCBEH)-B-(R) C18 1.7 m, 2.1 x 50 mm column. Sample run time was 3.0 min. The validation parameters: accuracy, precision and recovery were within recommended limits. Losartan as well as internal standard remains stable in benchtop stability study as well as in post-preparative stability study. Pharmacokinetic parameters such as Cmax (182.79 +/- 23.80 ng/mL), Tmax (1.16 +/- 0.28 h), AUC0-t (1188.57 +/- 404.60 ng h/mL) and Kel (0.0954 +/- 0.0140 h(-1)) of losartan were measured. Method was successfully applied for pharmacokinetic investigation in rabbits and can be used for losartan determination in plasma sample obtained from other animals.