A validated surrogate analyte UPLC-MS/MS assay for quantitation of TUDCA, TCDCA, UDCA, and CDCA in rat plasma: application in a pharmacokinetic study of cultured bear bile powder.
Biomed Chromatogr. 2020 Mar 21;:e4835
Authors: Zan B, Liu X, Zhao Y, Shi R, Sun X, Wang T, Li Y, Liu S, Yang L, Ma Y
Bear bile is a valuable medicinal material used in traditional Chinese medicine for over 2000 years. However, developing a substitute has become exceptionally urgent because of endangered species protection measures. In vitro cultured bear bile powder (CBBP) has ingredients, including TUDCA, TCDCA, UDCA, and CDCA, and pharmacological properties that are similar to those of natural bear bile powder (NBBP). In this study, pharmacokinetic parameters of both CBBP and NBBP were measured in rats with a new surrogate analyte LC-MS method using stable isotopes as surrogate analytes (D4-TUDCA, D4-TCDCA, D4-UDCA, and D4-CDCA) with response factors validated in authentic matrix (plasma) for simultaneously monitoring the authentic analytes (TUDCA, TCDCA, UDCA, and CDCA). The method validation was satisfactory for the linear regression (r, 0.9975-0.9994), precision (RSD intra-day, 0.72%-9.35%; inter-day, 3.82%-9.02%), accuracy (RE, -12.42%-5.67%), and matrix effect (95.53%-99.80%), along with analyte recovery (95.90%-98.82%) and stability (89.48%-101.81%) of surrogate analytes, and precision (RSD intra-day, 1.06%- 11.51%; inter-day, 2.23%- 11.38%), accuracy (RE, -7.40%-10.76%) and stability (87.37%-111.70%) of authentic analytes. We successfully applied this method to evaluate the pharmacokinetics of CBBP and NBBP in rats, which revealed critical in vivo properties of both bear bile preparations.
PMID: 32198899 [PubMed – as supplied by publisher]