Simultaneous quantification of 37 constituents in Duliang Pill by UPLC-MS/MS: Application to the pharmacokinetic studies in rat plasma

doi:10.5246/jcps.2023.07.047

Abstract

Abstract:

Duliang Pill (DLP), consisting of Baizhi and Chuanxiong, is the classical formula of traditional Chinese medicine. In order to investigate the substance basis of DLP, we developed a highly sensitive and reliable UPLC-MS/MS method capable of simultaneously detecting 37 constituents from both Baizhi and Chuanxiong. To achieve chromatographic separation, we utilized a Diamonsil C₁₈ column along with a mobile phase consisting of acetonitrile and 0.05% formic acid in water. MS analysis was conducted in the multiple reaction monitoring mode, utilizing electrospray ionization in either the positive or negative mode, depending on the compound being analyzed. The method was validated for specificity, linearity, sensitivity, precision, accuracy, recovery, matrix effect, and stability, and found to be satisfactory. The validated method was then applied to a pharmacokinetic study in rat plasma following oral administration of DLP extract. Our findings revealed that all compounds were rapidly absorbed from the gastrointestinal tract into the plasma, with most being eliminated completely within 24 h. Notably, coumarins derived from Baizhi exhibited superior oral absorption effects compared to ligustilides from Chuanxiong. Furthermore, we observed that the elimination of coumarins from Baizhi within DLP was slower compared to their elimination in single Baizhi. These results provided valuable insights for the overall study of active substances within the DLP formula and further research into the interaction mechanisms of Baizhi-Chuanxiong compatibility.

Key words: Duliang Pill, Baizhi, Chuanxiong, UPLC-MS/MS, Pharmacokinetics

Supporting:

Yanfang Yang, Wei Wei, Lei Zhang, Wei Xu, Xiuwei Yang. Simultaneous quantification of 37 constituents in Duliang Pill by UPLC-MS/MS: Application to the pharmacokinetic studies in rat plasma[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(7): 560-573.

Figures/Tables 6

Table 1. MW, precursor/product ion, and mass parameters of the 37 analytes and daidzein (IS).

Table 2. Intra- and inter-day precisions and accuracies, recoveries, stabilities, and matrix effects of the 37 analytes in rat plasma (mean ± SD, n = 6).

Table 3. Pharmacokinetics parameters of the 37 analytes in rat plasma (mean ± SD, n = 5).

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