Quantification of peramivir in rat plasma by liquid chromatography/tandem mass spectrometry employing precolumn derivatization and its application in pharmacokinetics
- VernacularTitle:衍生化LC-MS/MS测定大鼠血浆中新型抗流感药物帕拉米韦及其在药代动力学研究中的应用
- Author:
Ying, LI
;
Li-Li, WANG
;
Zhen-Qing, ZHANG
- Publication Type:Journal Article
- Keywords:
derivatization;
LC-MS/MS;
rat plasma;
peramivir;
neuraminidase inhibitor
- From:Bulletin of The Academy of Military Medical Sciences
2009;33(6):539-542
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To develop a liquid chromatography/tandem mass spectrometry employing precolumn derivatization method for determination of peramivir in rat plasma.Methods: The sample preparation consisted of a protein precipitation extraction followed by derivatization with hydrochloric acid (10 mol/L) methanol (10∶90, v/v) and determined by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The positive ion SRM mode was performed and the precursor-to-the-product ion transitions of m/z 343→284 and 299→152 were used to measure the derivative of peramivir and Ro 64-0802 (I.S.). The chromatographic separation was achieved using a Zorbax RX-C8 (2.1 mm × 150 mm × 5 μm) analytical column with an isocratic mobile phase composed of acetonitrile-water-formic acid (30∶70∶0.1, v/v/v, 0.2 ml/min). Results:The method was linear over a concentration range of 10 to 10 000 ng/ml. The LLOQ was 10 ng/ml. The average inter-day/intra-day precision values ranged from 5.0% to 7.1%, respectively, while the accuracy values ranged from 89.9% to 106.1%.Conclusion: In this method, retention time is greatly improved, the matrix effects are decreased by chemical derivatization. This method has been successfully applied to the preclinical and clinical research of peramivir.