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对映体选择性超临界流体色谱-串联质谱法同时测定大鼠血浆中利培酮及其9-羟基代谢物

Enantioselective supercritical fluid chromatography-tandem mass spectrometry method for simultaneous estimation of risperidone and its 9-hydroxyl metabolites in rat plasma.

作者信息

Prasad Thatipamula R, Joseph Siji, Kole Prashant, Kumar Anoop, Subramanian Murali, Rajagopalan Sudha, Kr Prabhakar

机构信息

Pharmaceutical Candidate Optimization, Biocon Bristol-Myers Squibb R&D Center (BBRC), Syngene International Limited, Biocon Park, Plot 2 & 3, Bommasandra IV Phase, Bangalore - 560099, India.

Market Development Centre, Agilent Technologies India Pvt. Ltd, ITPL Road, Mahadevapura, Bangalore - 560048, India.

出版信息

Bioanalysis. 2017 Nov;9(22):1739-1750. doi: 10.4155/bio-2017-0168. Epub 2017 Nov 9.

Abstract

AIM

Objective of the current work was to develop a 'green chemistry' compliant selective and sensitive supercritical fluid chromatography-tandem mass spectrometry method for simultaneous estimation of risperidone (RIS) and its chiral metabolites in rat plasma. Methodology & results: Agilent 1260 Infinity analytical supercritical fluid chromatography system resolved RIS and its chiral metabolites within runtime of 6 min using a gradient chromatography method. Using a simple protein precipitation sample preparation followed by mass spectrometric detection achieved a sensitivity of 0.92 nM (lower limit of quantification). With linearity over four log units (0.91-7500 nM), the method was found to be selective, accurate, precise and robust.

CONCLUSION

The method was validated and was successfully applied for simultaneous estimation of RIS and 9-hydroxyrisperidone metabolites (R & S individually) after intravenous and per oral administration to rats.

摘要

目的

本研究的目的是开发一种符合“绿色化学”的选择性和灵敏的超临界流体色谱 - 串联质谱法,用于同时测定大鼠血浆中的利培酮(RIS)及其手性代谢物。

方法与结果

安捷伦1260 Infinity分析型超临界流体色谱系统采用梯度色谱法,在6分钟的运行时间内分离出RIS及其手性代谢物。采用简单的蛋白沉淀样品制备方法,随后进行质谱检测,灵敏度达到0.92 nM(定量下限)。该方法在四个对数单位(0.91 - 7500 nM)范围内呈线性,具有选择性、准确性、精密度和稳健性。

结论

该方法经过验证,并成功应用于大鼠静脉注射和口服给药后RIS和9 - 羟基利培酮代谢物(分别为R和S)的同时测定。

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