[Pharmacokinetic comparison between Tanreqing Capsules Substitute and Tanreqing Capsules in rats by LC-MS/MS]

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Analytical Chemistry
• Traditional Chinese Medicine

Background:

• Tanreqing Capsules (TRQ), a key traditional Chinese medicine, faces resource limitations due to the scarcity of natural bear bile powder.
• Cultured bear bile powder has been developed as a sustainable alternative raw material for TRQ, leading to the formulation of Tanreqing Capsules Substitute (TRQS).
• Evaluating the pharmacokinetic equivalence of TRQS to TRQ is crucial for ensuring its therapeutic efficacy and safety.

Purpose of the Study:

• To develop and validate a sensitive LC-MS/MS method for the simultaneous quantification of eight key compounds in rat plasma after TRQS administration.
• To compare the pharmacokinetic profiles of TRQ and TRQS in rats to establish the bioequivalence of the substitute formulation.

Main Methods:

• An LC-MS/MS method was established for simultaneous quantitation of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA), ferulic acid, wogonoside, baicalin, and forsythoside A in rat plasma.
• Stable isotope surrogate analytes (D4-TUDCA, D4-TCDCA, D4-UDCA, D4-CDCA) were used for accurate quantification of endogenous bile acids.
• Plasma samples were prepared using acetonitrile-induced protein precipitation, and analysis was performed on a Waters BEH C18 column with a gradient elution of ammonium formate and acetonitrile-methanol mixture.

Main Results:

• The developed LC-MS/MS method demonstrated excellent linearity (r > 0.9951), accuracy (RE 89.98%-112.0%), precision (inter-day RSD < 7.0%), recovery (64.83%-119.9%), and matrix effect (87.15%-113.8%).
• Pharmacokinetic studies revealed no significant differences in maximum concentration (Cmax) and area under the curve (AUC0-24h) for baicalin, UDCA, TUDCA, and TCDCA between TRQ and TRQS groups.
• These findings indicate comparable absorption, distribution, metabolism, and excretion profiles for the key components of both formulations.

Conclusions:

• The validated LC-MS/MS method provides a reliable tool for pharmacokinetic analysis of TRQS components in biological matrices.
• TRQS exhibits similar pharmacokinetic behaviors to TRQ in rats, supporting its potential as an effective and sustainable alternative.
• This study validates the use of cultured bear bile powder in TRQS, ensuring comparable therapeutic outcomes to traditional TRQ.