Plasma pharmacokinetics and tissue distribution study of roemerine in rats by liquid chromatography with tandem mass spectrometry (LC–MS/MS)

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 969; pp. 249 - 255
• Main Authors: Liu, Yue-Qiong, He, Gong-Hao, Li, Hong-Liang, He, Jiang-Chang, Feng, En-Fu, Bai, Lan, Wang, Cheng-Ying, Xu, Gui-Li
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.10.2014
• Subjects: Alkaloids - blood; Alkaloids - chemistry; Alkaloids - pharmacokinetics; Animals; Chromatography, High Pressure Liquid - methods; Drug Stability; Female; LC–MS/MS; Linear Models; Male; Pharmacokinetics; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Roemerine; Sensitivity and Specificity; Tandem Mass Spectrometry - methods; Tissue Distribution; Tissue distribution; Pharmacokinetics; LC–MS/MS; Roemerine
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2014.08.031

•A new LC–MS/MS method for quantitation of roemerine in rat plasma and tissues was developed for the first time.•This method was fully validated according to FDA guidelines over the concentration range from 10 to 2000ng/mL.•The method developed has been demonstrated to be applicable for the measurement of roemerine in rat plasma and tissues.•This is the first report to evaluate the pharmacokinetics and distribution of roemerine. In the present study, a new LC–MS/MS method for the determination of roemerine in rat plasma and tissue samples was developed and successfully used to study the pharmacokinetics and tissue distribution of roemerine after oral and intravenous (i.v.) administration in rats. The plasma and tissue samples were processed by liquid–liquid extraction with n-hexane. Isocorydine was used as the internal standard (IS) for sample processing and analysis. The MS/MS detection was carried out by monitoring the transitions of m/z 280→249 and m/z 342→279 for roemerine and the IS, respectively. The calibration curve displayed excellent linearity over the concentration range of 10–2000ng/mL (n=8, r2≥0.995), and the lower limit of quantification (LLOQ) was determined to be 10ng/mL. This method was rapid, accurate, highly sensitive, and fully validated. The pharmacokinetic study showed that roemerine was rapidly absorbed and eliminated with a tmax of 0.22±0.08h, t1/2 of 1.59±0.46h, CL of 4.44±0.42L/h/kg, and Vd of 10.16±2.95μg/L following oral administration. Additionally, roemerine showed an excellent oral bioavailability of 84% and a wide tissue distribution with brain penetration. Highest concentrations of roemerine were found in the liver and lung, followed by kidney, spleen, heart, and brain, in that order.