Development of a validated UPLC-MS/MS method for determination of humantenmine in rat plasma and its application in pharmacokinetics and bioavailability studies

被引:14
作者
Hu, Yanxian [1 ]
Chen, Minghao [1 ]
Wang, Zhaoyu [1 ]
Lan, Yao [1 ]
Tang, Lan [1 ]
Liu, Menghua [1 ]
Zhao, Jie [1 ]
Hu, Ming [2 ]
Zhang, Lulu [3 ]
Ye, Ling [1 ]
机构
[1] Southern Med Univ, Guangdong Prov Key Lab New Drug Screening, Sch Pharmaceut Sci, Dept Biopharmaceut,State Key Lab Organ Failure Re, Guangzhou, Guangdong, Peoples R China
[2] Univ Houston, Coll Pharm, Dept Pharmacol & Pharmaceut Sci, Houston, TX 77030 USA
[3] Nanjing Med Univ, Sch Publ Hlth, Minist Educ, Dept Toxicol,Key Lab Modern Toxicol, Nanjing 211166, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
bioavailability; humantenmine; pharmacokinetics; UPLC-MS/MS; GELSEMIUM-ELEGANS BENTH; ALKALOIDS;
D O I
10.1002/bmc.4017
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Humantenmine (HMT), the most toxic compound isolated from Gelsemium elegans Benth, is a well-known active herbal compound. A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to estimate the absolute oral bioavailability of HMT in rats. Quantification was performed by multiple reaction monitoring using electrospray ionization operated in positive ion mode with transitions of m/z 327.14m/z 296.19 for HMT and m/z 323.20m/z 236.23 for gelsemine (internal standard, IS). The linear range of the calibration curve was 1-256nmol/L, with a lower limit of quantification at 1nmol/L. The accuracy of HMT ranged from 89.39 to 107.5%, and the precision was within 12.24% (RSD). Excellent recovery and negligible matrix effect were observed. HMT remained stable during storage, preparation and analytical procedures. The pharmacokinetics of HMT in rats showed that HMT reached the concentration peak at 12.50 +/- 2.74min with a peak concentration of 28.49 +/- 6.65nmol/L, and the corresponding area under the concentration-time curve (AUC(0-t)) was 1142.42 +/- 202.92nmol/L min after 200g/kg HMT was orally administered to rats. The AUC(0-t) of HMT given at 20g/kg by tail vein administration was 1518.46 +/- 192.24nmol/L min. The calculated absolute bioavailability of HMT was 7.66%.
引用
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页数:6
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