Abstract
An ultra-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) method for the simultaneous determination of Crocin-I and its primary metabolites Crocetin was established, and a comparison of metabolic characteristics in vivo is made to Crocin-I and Crocetin in normoxic and hypoxic rats after intragastric administration. The acute hypoxic rat model was established by simulating high altitude environment in a hypobaric hypoxia animal experimental chamber. After intragastric administration of 400 mg•kg−1 Crocin-I. UPLC-Q-TOF-MS method was used to detect the plasma concentrations of Crocin-I and Crocetin in plasma at different times. Compared with normoxic rats, the area under the curve (AUC), mean residence time (MRT), time to peak (Tmax), half-life (T1/2) and plasma concentration (Cmax) of plasma Crocin-I in hypoxic rats were significantly increased (P < 0.01). The apparent distribution (Vz/F) and clearance (CLz/F) of plasma Crocin-I in hypoxic rats were significantly decreased (P < 0.01). Under hypoxic conditions, the pharmacokinetic parameters of Crocin-I and its metabolite Crocetin change significantly. The results provide a theoretical basis for the feasibility of Crocin-I for anti-hypoxia treatment in terms of pharmacokinetics and provide an essential experimental basis for optimizing the drug dosing regimen.
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