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Archive > Volume 9 Issue 3 > 2017,9(3):236-249. DOI:10.1016/S1674-6384(17)60100-X Prev Next

Original articles

Sensitive Analysis and Pharmacokinetic Study of Berberrubine Using LC-MS/MS

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    摘要:


    Abstract:
    Objective To develop a sensitive and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to evaluate the pharmacokinetic behavior of berberrubine (BRB) and its glucuronide (BRBG) in rats. Methods BRB, BRBG and tetrahydroberberine (THB, internal standard) were isolated by liquid-liquid extraction in rat biological samples. Chromatographic separation was achieved on an Agilent Zorbax Eclipse Plus C18 (2.1 mm × 50 mm, 3.5-Micron) with a gradient mobile phases primarily containing acetonitrile, water with 0.1% formic acid and 5 mm ammonium acetate. The analytes were monitored by MS/MS in positive electrospray ionization mode. Herein, the feasibility of new developed method was validated with respect to specificity, linearity, precision, accuracy, stability, extraction efficiency and matrix effect. The appropriate method was used for the pharmacokinetic study in rats. Results The new developed method could be applied to the pharmacokinetic study of BRB in rats. BRB and BRBG showed good linearity over the ranges of 2-1000 ng/mL and 5-2000 ng/mL, respectively, and precision was no more than 15%. The accuracy, specificity and stability could be acceptable. Conclusion The new method is sensitive and reproducible. In pharmacokinetic study, BRB showed nonlinear elimination property. Meanwhile, BRB was rapidly absorbed and widely distributed in various tissues with the highest exposure of BRB in kidney and liver. The absolute bioavailability of BRB was determined to be 8.2% and at the dose of 40 mg/kg, a total of 44% BRB was excreted in urine and feces.

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    Project Supported:
    National Natural Science Foundation of the People’s Republic of China (No. 81573495, 81530098); Key Technology Projects of China “Creation of New Drugs” (No. 2015ZX09501001); Project for Jiangsu Province Key Lab of Drug Metabolism and Pharmacokinetics (BM2012012)

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