Distribution of Nardosinone and Its Metabolites in Rats Analyzed by UPLC-Q-Exactive Orbitrap MS/MS

Abstract:

Objective Ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS/MS） was used to investigate the metabolism and distribution of nardosinone in rats， then metabolic pathways were speculated.Method Rats were administered with 30 mg·kg^-1 of nardosinone suspension by gavage for 3 consecutive days， and plasma， urine， feces， and tissues of heart， liver， spleen， lung， kidney， brain， stomach， and intestine were collected at predetermined time points. After treatment， the samples were processed for UPLC-Q-Exactive Orbitrap MS/MS， and the MS data were analyzed using Xcalibur 2.2 software. The metabolites were searched by comparing the base peak chromatogram and extracted ion chromatogram between the treated group and blank group， and based on the relative retention time（t_R）， quasi-molecular ion peak， precise molecular mass， and fragment ions of MS/MS， the elemental composition were searched using databases such as SciFinder and PubChem， as well as referring to relevant literature， the possible metabolites were identified and the metabolic pathways were inferred.Result A total of 30 metabolites of nardosinone were identified， including 15， 19， 12， 7， 4， 11， 8， 13， 13， 8 and 12 metabolites in urine， feces， plasma， brain， heart， liver， spleen， lung， kidney， stomach and intestine， respectively. The main metabolic pathways of nardosinone in rats were hydroxylation， dehydroxylation， reduction， dehydrogenation， hydration， dehydration， carboxylation， glucuronidation， and dehydroxy-isopropyl.Conclusion Nardosinone can be metabolized by phase Ⅰ and phase Ⅱ metabolism in rats， and the metabolites are widely distributed in the major organs. The results of this study can provide a basis for further research on the pharmacodynamic material basis， pharmacological mechanism and clinical application of nardosinone.