Citation

Gergov M, Ketola RA. Forensic Toxicol. 2016; 34(2): 235-243.

Copyright

(Copyright © 2016, Holtzbrinck Springer Nature Publishing Group)

DOI

10.1007/s11419-016-0308-y

PMID

unavailable

Abstract

A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the analysis of seven common sartans (candesartan, eprosartan, losartan, olmesartan, telmisartan, valsartan, and losartan carboxylic acid (EXP3174), the active metabolite of losartan) in postmortem blood samples with liquid-liquid extraction. Detection was accomplished by triple-quadrupole MS in the selected reaction monitoring mode. The validation procedure showed low limits of quantitation of 5 ng/mL for all compounds with good accuracy and precision. The matrix effect was evaluated from the variation of peak areas and concentrations. The method shows some matrix effect but the effect was efficiently compensated by using an internal standard method. The method was applied to the analysis of sartans in postmortem blood samples, and produced 534 positive findings during 2014-2015. Nine deaths were encountered where the concentration of a sartan was very high, indicating intoxication together with other causes of death or multi-drug intoxication. The quantitative results indicate that sartans do not show significant postmortem redistribution; thus concentrations higher than the therapeutic range can be considered as being toxic or fatal. © 2016, Japanese Association of Forensic Toxicology and Springer Japan.

Language: en

Keywords

adult; human; suicide; female; male; aged; autopsy; drug overdose; clinical article; drug intoxication; liquid chromatography; validation process; priority journal; middle aged; drug blood level; drug determination; liquid liquid extraction; metoprolol; Article; losartan; olmesartan; amlodipine; tandem mass spectrometry; Postmortem; drug protein binding; valsartan; Blood concentration; very elderly; telmisartan; limit of quantitation; volume of distribution; measurement accuracy; 2 butyl 4 chloro 1 [[2' (1h tetrazol 5 yl) 4 biphenylyl]methyl] 5 imidazolecarboxylic acid; Angiotensin II receptor antagonists; candesartan; eprosartan; LC–MS/MS; measurement precision; sartan derivative; Sartans