Pharmacokinetic study on hirsutine and hirsuteine in rats using UPLC–MS/MS

Acta Chromatographicae

Wu Qing¹  Lin Guanyang²  Han Aixia³  Cai Jinzhang⁴ 

[1] Analytical and Testing Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035;Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000;Department of Pharmacy, The People's Hospital of Lishui, Lishui 323000;The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027

关键词: Hirsutine;    hirsuteine;    pharmacokinetics;    UPLC–MS/MS;    bioavailability;   

DOI  :  10.1556/1326.2017.00365

学科分类：化学（综合）

来源: Akademiai Kiado Rt.

【 摘 要 】

An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was established to determine hirsutine and hirsuteine in rat plasma. Pharmacokinetics of hirsutine and hirsuteine in rats after intravenous or oral administration has been investigated using this developed UPLC–MS/MS method, and bioavailability of the two drugs was calculated. Diazepam was used as internal standard, and UPLC BEH column (2.1 mm × 50 mm, 1.7 μm) was used at temperature of 40 °C. The mobile phase was composed of acetonitrile and water (containing 0.1% formic acid) at a gradient elution flow rate of 0.4 mL/min. Nitrogen was used as desolvation gas (800 L/h) and conical gas (50 L/h). The multiple reaction monitoring (MRM) model was applied to quantitatively analyze hirsutine m/z 369 → 226, hirsuteine m/z 367 → 169.9, and diazepam (internal standard) m/z 285.1 → 193.3. Rat plasma samples were deproteinized using acetonitrile prior to UPLC–MS/MS analysis. Within the concentration range of 1–200 ng/mL, the linearity of hirsutine and hirsuteine in plasma was good (r > 0.995), and the lower limit of quantitation was 1 ng/mL. Relative standard deviations of intra-day precision for hirsutine and hirsuteine were ≤6.1% and ≤5.9%, respectively, and those of inter-day precision were ≤6% and ≤7.7%. Accuracy for hirsutine and hirsuteine ranged between 92.3% and 104.8%. Bioavailability of hirsutine and hirsuteine was 4.4% and 8.2%, respectively. The method is sensitive and fast with good selectivity and was successfully applied in the pharmacokinetic studies after intravenous and oral administration of hirsutine and hirsuteine.

【 授权许可】

Unknown