Determination of methylphenidate and ritalinic acid in blood, plasma and oral fluid from adolescents and adults using protein precipitation and liquid chromatography tandem mass spectrometry-A method applied on clinical and forensic investigations

被引:33
作者
Josefsson, Martin [1 ,2 ]
Rydberg, Irene [3 ]
机构
[1] Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, SE-58158 Linkoping, Sweden
[2] Linkoping Univ, Dept Phys Chem & Biol, SE-58183 Linkoping, Sweden
[3] Linkoping Univ, Fac Hlth Sci, Div Drug Res, Dept Med & Hlth Sci, SE-58185 Linkoping, Sweden
基金
瑞典研究理事会;
关键词
Methylphenidate; Ritalinic acid; Blood; Oral fluid; LC-MS/MS; DEFICIT-HYPERACTIVITY DISORDER; PHARMACOKINETICS; FORMULATION; EXTRACTION; METABOLITE; SAMPLES; ABUSE; PHASE; SWEAT;
D O I
10.1016/j.jpba.2011.03.009
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
A validated, accurate and sensitive LC-MS/MS method for determination of racemic methylphenidate and its metabolite ritalinic acid has been developed. The analytes were quantified by tandem mass spectrometry operating in positive electrospray ionization mode with multiple reaction monitoring. Blood, plasma and oral fluid samples of 100 mu l were prepared by simple precipitation with 200 RI of an aqueous solution of zinc sulphate in methanol. Corresponding deuterated internal standards were used for quantification. Calibrations for methylphenidate and ritalinic acid were linear within the selected range of 0.2-30 ng/ml and 10-1500 ng/ml in blood or plasma and in the range of 1-500 ng/ml and 0.25-125 ng/ml in oral fluid, respectively. The method was successfully applied for the analysis of samples from patients treated with methylphenidate in the dose range of 36-72 mg/day and some representative ante mortem and post mortem samples from clinical and forensic toxicological investigations. A three to fourfold higher concentration of methylphenidate was found in oral fluid compared with blood while for ritalinic acid the concentrations were about 25-fold lower in oral fluid. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:1050 / 1059
页数:10
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