Accuracy Profile Theory for the Validation of an LC–MS-MS Method for the Determination of Risperidone and 9-Hydroxyrisperidone in Human Plasma 2010, 71, 1015–1023
Xianhua Zhang1, Xia Zhao2, Chao Zhang1, Li Yang1, Xin Xiong1, Yong Zhou1, Yiheng Yang1, Jingli Duan1,& 1 2
Department of Pharmacy, Peking University Third Hospital, Beijing 100191, People’s Republic of China; E-Mail:
[email protected] Department of Pharmacy, Peking University First Hospital, Beijing 100034, People’s Republic of China
Received: 3 January 2010 / Revised: 10 March 2010 / Accepted: 15 March 2010 Online publication: 24 April 2010
Introduction
Abstract A sensitive and specific LC–MS-MS method is described for the simultaneous quantification of risperidone and 9-hydroxyrisperidone in human plasma. After extraction with tert-butyl methyl ether, plasma samples were separated on an Atlantis HILIC Silica C18 column (4.6 9 150 mm, 5 lm)with a mobile phase of ammonium formate buffer (10 mM, pH 4.0)/ acetonitrile (40/60, v/v). Detection was by MS-MS. The method was fully validated according to the accuracy profile theory. It is based on b-expectation tolerance interval for the total measurement error which includes trueness and intermediate precision. The measurement uncertainty derived from b-expectation tolerance interval was estimated at each of the validation standards. The linearity fitted well over the range of 0.11–26.75 ng mL-1 for risperidone with an LLOQ of 0.11 ng mL-1, and for 9-hydroxyrisperidone, at a range of 0.15–37.8 ng mL-1 with an LLOQ of 0.15 ng mL-1. The intra- and inter-batch precision of risperidone were
