Shah Priyanka A, Shrivastav Pranav S
Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad, India.
Biomed Chromatogr. 2018 Feb;32(2). doi: 10.1002/bmc.4041. Epub 2017 Jul 25.
A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is described for the simultaneous determination of silodosin (SLD) and its active metabolite silodosin β-d-glucuronide (KMD-3213G) in human plasma. Liquid-liquid extraction of plasma samples was carried out with ethyl acetate and methyl tert-butyl ether solvent mixture using deuterated analogs as internal standards. The extraction recoveries of SLD and KMD-3213G were in the ranges 90.8-93.4 and 87.6-89.9%, respectively. The extracts were analyzed on a Symmetry C (50 × 4.6 mm, 5 μm) column under gradient conditions using 10 mm ammonium formate in water and methanol-acetonitrile (40:60, v/v), within 6.0 min. For MS/MS measurements, ionization of the analytes was carried out in the positive ionization mode and the transitions monitored were m/z 496.1 → 261.2 for SLD and m/z 670.2 → 494.1 for KMD-3213G. The method showed good linearity, accuracy, precision and stability in the range 0.10-80.0 ng/mL for SLD and KMD-3213G. The IS-normalized matrix factors obtained were highly consistent, ranging from 0.962 to 1.023 for both analytes. The method was used to support a bioequivalence study of SLD and its metabolite in healthy volunteers after oral administration of 8 mg silodosin capsules.
描述了一种灵敏且具选择性的液相色谱 - 串联质谱法（LC-MS/MS），用于同时测定人血浆中的西洛多辛（SLD）及其活性代谢物西洛多辛β - D - 葡萄糖醛酸苷（KMD - 3213G）。以氘代类似物作为内标，采用乙酸乙酯和甲基叔丁基醚混合溶剂对血浆样品进行液 - 液萃取。SLD和KMD - 3213G的萃取回收率分别在90.8 - 93.4%和87.6 - 89.9%范围内。萃取物在Symmetry C（50×4.6 mm，5μm）柱上，于梯度条件下进行分析，流动相为含10 mM甲酸铵的水溶液和甲醇 - 乙腈（40:60，v/v），在6.0分钟内完成分离。对于MS/MS测定，分析物在正离子模式下进行电离，监测的离子跃迁为：SLD的m/z 496.1→261.2，KMD - 3213G的m/z 670.2→494.1。该方法在0.10 - 80.0 ng/mL范围内对SLD和KMD - 3213G表现出良好的线性、准确性、精密度和稳定性。获得的内标归一化基质因子高度一致，两种分析物的范围均为0.962至1.023。该方法用于支持在健康志愿者口服8 mg西洛多辛胶囊后对SLD及其代谢物进行的生物等效性研究。
