A sensitive and specific ultra-performance liquid chromatographic–tandem mass spectrometric method was developed and validated to simultaneously determine periplocin, periplocymarin (PM), periplogenin (PG), periplocoside M (PSM) and periplocoside N (PSN) in rat plasma. Acetonitrile was employed to precipitate plasma with appropriate sensitivity and acceptable matrix effects. Chromatographic separation was performed using a Waters HSS T3 column with a gradient elution using water and acetonitrile both containing 0.1% formic acid and 0.1 mm ammonium formate within 8 min. Detection was performed in positive ionization mode using multiple reaction monitoring. The method was fully validated in terms of selectivity, linearity, accuracy, precision, recovery, matrix effects and stability. Using this method, the concentrations of periplocin, PM, PG, PSM and PSN were established after oral administration of Cortex Periplocae extract to rats, and the pharmacokinetic characteristics of periplocin, PM, PG, PSM and PSN were assessed. Generally, PM, PG, PSM and PSN were eliminated slowly and their half-lives were all >8 h. In addition, the systemic exposure of PSM showed significant differences between genders with more than 10 times higher area under the concentration–time curve in female rats than in male rats. The findings of this study provide useful information for further research on Cortex Periplocae.

中文翻译：

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同时测定大鼠血浆中外周皮层中的外周素、外周香脂素、外周素、外周甙M和外周甙N及其在药代动力学研究中的应用

开发并验证了一种灵敏且特异的超高效液相色谱-串联质谱方法，可同时测定大鼠血浆中的 periplocin、periplocymarin (PM)、periplogenin (PG)、periplocoside M (PSM) 和 periplocoside N (PSN)。乙腈用于以适当的灵敏度和可接受的基质效应沉淀血浆。使用 Waters HSS T3 色谱柱进行色谱分离，使用水和乙腈进行梯度洗脱，均含有 0.1% 甲酸和 0.1 m m8 分钟内得到甲酸铵。使用多反应监测在正离子模式下进行检测。该方法在选择性、线性、准确度、精密度、回收率、基质效应和稳定性方面得到了充分验证。采用该方法，建立大鼠口服黄连皮提取物后的periplocin、PM、PG、PSM和PSN的浓度，并评估periplocin、PM、PG、PSM和PSN的药代动力学特征。一般而言，PM、PG、PSM和PSN消除较慢，半衰期均>8 h。此外，PSM 的全身暴露表现出性别之间的显着差异，雌性大鼠的浓度-时间曲线下面积比雄性大鼠高 10 倍以上。