We developed and validated a simple, sensitive, selective, and reliable LC–MS/MS–ESI method for the direct quantitation of lumefantrine (LFN) enantiomers [(−)‐LFN and (+)‐LFN] in mice plasma as per regulatory guideline. LFN enantiomers and carbamazepine (internal standard) were extracted from mice plasma using Strata X SPE (solid‐phase extraction) cartridges. Good resolution between enantiomers was achieved on a Chiralpak IA‐3 column using an isocratic mobile phase (0.1% of diethyl amine in methanol), which was delivered at a flow rate of 0.8 mL/min. Detection and quantitation were performed using multiple reaction monitoring mode following the transitions m/z 530.27 → 512.30 and 237.00 → 194.00 for LFN enantiomers and the internal standard, respectively, in the positive‐ionization mode. The proposed method provided accurate and reproducible results over the linearity range of 2.39–895 ng/mL for each enantiomer. The intra‐ and inter‐day precisions were in the range of 1.03–6.14 and 6.36–8.70 and 2.03–4.88 and 5.82–11.5 for (−)‐LFN and (+)‐LFN, respectively. Both (−)‐LFN and (+)‐LFN were found to be stable under different stability conditions. The method was successfully used to delineate stereoselective pharmacokinetics of LFN enantiomers in mice after an oral administration of rac‐LFN (20 mg/kg). The pharmacokinetic results indicated that the disposition of LFN enantiomers was stereoselective in mice.

中文翻译：

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对映体选择性LC-ESI-MS / MS方法用于定量测定小鼠血浆中的（-）-黄连精和（+）-黄连精，并将其用于药代动力学研究。

我们开发并验证了一种简单，灵敏，选择性和可靠的LC-MS / MS-ESI方法，可根据法规对小鼠血浆中的卢富汀（LFN）对映异构体[（-）-LFN和（+）-LFN]直接定量准则。使用Strata X SPE（固相萃取）柱从小鼠血浆中萃取LFN对映异构体和卡马西平（内标）。使用等度流动相（0.1％的二乙胺的甲醇溶液）在Chiralpak IA-3色谱柱上实现对映体之间的良好分离，流速为0.8 mL / min。在转换m / z时使用多种反应监测模式进行检测和定量对于LFN对映异构体和内标，在正电离模式下分别为530.27→512.30和237.00→194.00。所提出的方法在每种对映异构体的2.39–895 ng / mL线性范围内提供了准确且可重复的结果。（-）-LFN和（+）-LFN的日内和日间精度分别在1.03-6.14和6.36-8.70和2.03-4.88和5.82-11.5之间。发现（-）-LFN和（+）-LFN在不同的稳定性条件下都是稳定的。口服rac -LFN（20 mg / kg）后，该方法已成功用于描述LFN对映异构体在小鼠中的立体选择性药代动力学。药代动力学结果表明，LFN对映体在小鼠体内具有立体选择性。