Simultaneous high‐performance liquid chromatography with tandem mass spectrometry quantification of six bioactive components in rat plasma after oral administration of Yougui pill

Abstract

Yougui pills are a classic Chinese medicine that shows significant effects on nerve regeneration and neuroprotection in modern pharmacological studies. With a complex formula, Yougui pills have faced significant challenges in the fields of bioanalysis and pharmacokinetics in animals and human studies. In the present study, a specific and accurate high‐performance liquid chromatography with tandem mass spectrometry method was developed and validated for the quantitative determination of the six bioactive components in rat plasma after oral administration of Yougui pills. Chromatographic separation was performed on a C18 column with a gradient elution system. Samples were analysed using positive ion mode with multiple reaction monitoring mode. The assay showed good linearity for all six bioactive components in the dynamic range of 0.50 to 50 ng/mL with acceptable intra‐ and inter‐batch accuracy and precision. The lower limits of quantification were 0.50 ng/mL for all six bioactive components. The method was successfully applied to rat pharmacokinetics after oral administration of Yougui pills. All six bioactive components were detected in rat plasma, including songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline, and sweroside, while some other target compounds were not detected, such as rhmannioside A, loganin, and cornuside I. After oral administration of Yougui pills at a dose of 2500 mg/kg, all six bioactive components were rapidly absorbed, resulting in tmax values less than 1 h and relative lower Cmax values. The t1/2 values for songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline, and sweroside were calculated to be 2.62 ± 0.67, 2.11 ± 0.45, 1.94 ± 0.35, 1.88 ± 0.31, 2.07 ± 0.44, and 1.59 ± 0.30 h, which indicated that Yougui pills should be taken in multiple oral doses over a relatively short period.

Development of an ultra‐high‐performance liquid chromatography–tandem mass spectrometry method for the simultaneous determination of crassicauline A, fuziline, karacoline, and songorine in rat plasma and application in their pharmacokinetics

“…After the oral administration of Yougui pills at a dose of 2500 mg/kg, songorine and karacoline were rapidly absorbed, resulting in t max values less than 1 h and relatively low C max values. The t 1/2 values for songorine and karacoline were calculated as 2.62 ± 0.67 and 2.07 ± 0.44 h, respectively, according to Liu et al (2019). The results align with the findings of our study.…”

“…Li et al, (2014) developed and validated a UPLC–quadrupole time‐of‐flight–MS method for quantifying the levels of fuziline in rat plasma after oral administration of three dosages. Liu et al, (2019) developed and validated an LC–MS/MS method for the quantitative determination of the six bioactive components (songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline, and sweroside) in rat plasma after oral administration of Yougui pills. Tang et al, (2023) established and validated a simple and sensitive ultrafast LC with MS/MS method for the determination of aconine, mesaconine, hypaconine, deoxyaconine, and fuziline in rat plasma to compare the pharmacokinetic characteristics of pure amino alcohol–diterpenoid alkaloids and Fuzi decoction.…”