Simultaneous Determination of Six Components in Beagle Dog Plasma by UPLC-MS/MS and Its Application to a Comparative Pharmacokinetic Study of Three Different Yuanhu Zhitong Preparations

Abstract

This study has developed a sensitive, simple, and reliable ultrahigh performance liquid chromatography tandem mass spectrometry method for the simultaneous determination of corydaline, tetrahydropalmatine, tetrahydroberberine, tetrahydrocoptisine, byakangelicin, and byakangelicol in beagle dog plasma after oral administration of Yuanhu Zhitong (YHZT) oral liquid, dispersible tablet, and dropping pills. A one-step protein precipitation method was used with methanol-acetonitrile (50 : 50, v/v) for plasma sample pretreatment. Six analytes and one internal standard were separated on a Waters Acquity UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) by gradient elution with 0.1% formic acid-water and 0.1% formic acid-acetonitrile at a flow rate of 0.4 mL/min. Detection was conducted by multiple reaction monitoring mode in the positive ionization. The calibration curves showed good linearity (r > 0.9920). The lower limit of quantization ranged from 0.1 to 1 ng/mL. Moreover, the other results of the method validation were within the acceptable range. After oral administration, the pharmacokinetic characteristics of the three YHZT preparations were different. Compared with the two solid preparations, the absorption of the six analytes in oral liquid was more rapid. Moreover, the area under the plasma drug concentration-time curve and the maximum plasma concentration of tetrahydropalmatine (the main analgesic component of YHZT prescription) in the oral liquid group were higher than those in the other two groups. The results showed oral liquid can exert its efficacy quickly, while dispersible tablet and dropping pills exhibit relatively slow release pattern. The comparative pharmacokinetic study would be helpful to the clinical rational selection and application of YHZT preparations.