Simultaneous determination of benzoylmesaconine and piperine in rat plasma after oral administration of Naru-3 by an ultra fast liquid chromatography-tandem mass spectrometry method and its application in a comparative pharmacokinetic study

Abstract

A rapid, sensitive and reliable ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed for the simultaneous quantitation of benzoylmesaconine and piperine in rat plasma after oral administration of Naru-3. Naru-3 is a well-known traditional Mongolian medical analgesic formula, which contains three Chinese herb powders – Aconiti Kusnezoffii Radix Cocta, Piperis Longi Fructus and Chebulae Fructus. After addition of brucine (internal standard, IS), 100 μL of plasma was extracted by liquid–liquid extraction with methyl tert-butyl ether, and then the two analytes and IS were separated on a Venusil MP C18 column (100 mm × 2.1 mm, 3.0 μm) at 30 °C with a gradient program of 0.1% formic acid–methanol in water as the mobile phase. The UFLC-MS/MS system coupled with an electrospray ionization source was performed in multiple reaction monitoring mode. The linear range was 0.075–15 ng mL⁻¹ for benzoylmesaconine and 5–1000 ng mL⁻¹ for piperine. The linearity, accuracy, precision, recovery and matrix effect of the two analytes were all within satisfaction. The validated method was successfully applied to compare the pharmacokinetic profiles of the analytes in rat plasma after oral administration of three compatibility-composition suspensions designed according to the Naru-3 pill. The pharmacokinetic data obtained by this method indicated that some ingredients in the Naru-3 pill could have an influence on the pharmacokinetic behavior of the two analytes.