TY - JOUR
T1 - Enantioselective determination of methylphenidate and ritalinic acid in whole blood from forensic cases using automated solid-phase extraction and liquid chromatography-tandem mass spectrometry
AU - Thomsen, Ragnar
AU - Rasmussen, Henrik B.
AU - Linnet, Kristian
AU - Jürgens, Gesche
AU - Dalhoff, Kim
AU - Stage, Claus
AU - Stefansson, Hreinn
AU - Hankemeier, Thomas
AU - Kaddurah-Daouk, Rima
AU - Brunak, Søren
AU - Taboureau, Olivier
AU - Houmann, Tine
AU - Jeppesen, Pia
AU - Kaalund-Jørgensen, Kristine
AU - Rindel, Louise
AU - Hansen, Peter Riis
AU - Pagsberg, Anne Katrine
AU - Plessen, Kerstin
AU - Hansen, Poul Erik
PY - 2012/10/25
Y1 - 2012/10/25
N2 - A chiral liquid chromatography tandem mass spectrometry (LC-MS-MS) method was developed and validated for quantifying methylphenidate and its major metabolite ritalinic acid in blood from forensic cases. Blood samples were prepared in a fully automated system by protein precipitation followed by solid-phase extraction. The LC-MS-MS method was linear in the range of 0.5 to 500 ng/g for the enantiomers of both analytes. For concentrations above the limit of quantification, coefficients of variation were 15% or less, and the accuracy was 89 to 94%. For 12 postmortem samples in which methylphenidate was not determined to be related to the cause of death, the femoral blood concentration of d-methylphenidate ranged from 5 to 58 ng/g, and from undetected to 48 ng/g for l-methylphenidate (median d/l-ratio 5.9). Ritalinic acid was present at concentrations 10-20 times higher with roughly equal amounts of the d- and l-forms. In blood from 10 living subjects that were not suspected of being intoxicated by methylphenidate, the concentration ranges and patterns were similar to those of the postmortem cases. Thus, methylphenidate does not appear to undergo significant postmortem redistribution.
AB - A chiral liquid chromatography tandem mass spectrometry (LC-MS-MS) method was developed and validated for quantifying methylphenidate and its major metabolite ritalinic acid in blood from forensic cases. Blood samples were prepared in a fully automated system by protein precipitation followed by solid-phase extraction. The LC-MS-MS method was linear in the range of 0.5 to 500 ng/g for the enantiomers of both analytes. For concentrations above the limit of quantification, coefficients of variation were 15% or less, and the accuracy was 89 to 94%. For 12 postmortem samples in which methylphenidate was not determined to be related to the cause of death, the femoral blood concentration of d-methylphenidate ranged from 5 to 58 ng/g, and from undetected to 48 ng/g for l-methylphenidate (median d/l-ratio 5.9). Ritalinic acid was present at concentrations 10-20 times higher with roughly equal amounts of the d- and l-forms. In blood from 10 living subjects that were not suspected of being intoxicated by methylphenidate, the concentration ranges and patterns were similar to those of the postmortem cases. Thus, methylphenidate does not appear to undergo significant postmortem redistribution.
UR - http://www.scopus.com/inward/record.url?scp=84867679890&partnerID=8YFLogxK
U2 - 10.1093/jat/bks065
DO - 10.1093/jat/bks065
M3 - Article
C2 - 22833645
AN - SCOPUS:84867679890
SN - 0146-4760
VL - 36
SP - 560
EP - 568
JO - Journal of Analytical Toxicology
JF - Journal of Analytical Toxicology
IS - 8
ER -