A rapid and effective method using QuEChERS-based sample preparation procedure and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis has been developed and validated to determine progesterone in rabbit plasma. The analyte was extracted from plasma by acetonitrile with phase partitioning by a mixture of magnesium sulfate and sodium chloride. The supernatant was then directly injected into LC-MS/MS in a positive electrospray ionization mode and quantified using progesterone-d9 as the internal standard. The method linearity was in the range from 1 ng/mL (LOQ) to 200 ng/mL. Method recovery was from 86.0% to 103%, and repeatability was lower than 5.5%. The plasma sample was stable for 12 weeks stored at 18 ± 2°C. This method was applied to quantify progesterone in rabbit plasma in a pharmacokinetic study of two transdermal formulations: a reference drug and a eutectic-hydrogel system. The data indicate that the eutectic-hydrogel system’s bioavailability was 1.5 times better than that of the reference drug, and the transdermal system is a potential drug delivery system for progesterone.

中文翻译：

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LC-MS / MS法快速定量兔血浆中的孕酮及其在透皮制剂药代动力学研究中的应用

已经开发出一种快速有效的方法，该方法使用基于QuEChERS的样品制备程序和液相色谱-串联质谱（LC-MS / MS）分析来确定兔血浆中的孕酮。通过乙腈从血浆中提取分析物，并通过硫酸镁和氯化钠的混合物进行相分配。然后将上清液以正电喷雾电离模式直接注入LC-MS / MS，并使用孕酮-d9作为内标进行定量。方法线性范围为1 ng / mL（LOQ）至200 ng / mL。方法回收率为86.0％至103％，重复性低于5.5％。血浆样品在18±2°C下稳定保存12周。在两种透皮制剂的药代动力学研究中，该方法用于定量兔血浆中的孕酮：参考药物和共晶水凝胶系统。数据表明，共晶水凝胶系统的生物利用度是参考药物的1.5倍，而透皮系统是孕激素的潜在药物传递系统。