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A rapid and sensitive UHPLC-MS/MS method for the determination of celosin A in rat plasma with application to
Jiawei Shen1, Xiuqin Cao1, Weili Zhou1
1Department of Clinical Pharmacology, Minhang Branch of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghgai University of Traditional Chinese Medicine, Shanghai, China.
Abstract:
Celosin A (CA), a natural compound isolated from Celosia argentea L., has been shown significant hepatoprotective effect on AHNP-induced liver injury. This study described a rapid and sensitive ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay for determination of CA in rat plasma. Methanol-mediated precipitation was used for sample pretreatment. Chromatographic separation was achieved on a T3 column with gradient elution using water and acetonitrile as mobile phase. Determination was obtained using an electrospray ionization source in negative selected reaction monitoring mode at the transitions of m/z 793.3 → m/z 661.2 and m/z 955.6 → m/z 793.2 for CA and IS, respectively. The assay was linear over the concentration range 0.25-2500 ng/mL (r > 0.995) with a lowest limit of quantification (LLOQ) of 0.25 ng/mL. The intra- and inter-day precisions (RSD) were 1.65-9.84 and 2.46-13.49%, respectively, while accuracy (RR) ranged from 96.21 to 99.45%, respectively. The recovery ranged from 95.09 to 102.22% and the matrix effect from 98.29 to 100.13%. The analyte was stable under the tested storage conditions. The method has been successfully applied to a preclinical pharmacokinetic study in rats after a single intravenous (2 mg/kg) or oral (50 mg/kg) administration. The oral bioavailability of CA was ~1.94%; in addition, there was no difference between male and female rats. This is the first time of the use of an UHPLC-MS/MS method for determination of CA concentration in rat plasma and for evaluation of its pharmacokinetic behavior.
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