Simultaneous Screening and Quantitation of Drugs and their Metabolites in Post-Mortem Vitreous Humor by Liquid Chromatography-High Resolution Mass Spectrometry.
Edmund Rab, Ellen Sellers, Marta-Sofia Lindo-Cardoso, Gabrielle Wall, Faizan Khan
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Abstract
Post-mortem vitreous humor may be used for toxicological analysis if blood and urine are unavailable, or where post-mortem blood is thought to be affected by post-mortem changes. Use of vitreous humor has been restricted by the available sample volume and instrument sensitivity. However, the advent of combined screening and quantitative methodologies using liquid chromatography-high resolution mass spectrometry (LC-HRMS) makes analysis of vitreous humor possible. This study examines an existing combined screening and quantitative methodology to determine if it is suitable for use with vitreous humor. Analysis of standard solutions containing 48 compounds showed % difference between expected and measured values in the range -15.59 to 20.81, -15.73 to 18.34, -14.32 to 19.77 and -19.90 to 19.78 for very low, low, mid and high range standard solutions respectively. Intraassay %CV was in the range 0.93 to 10.10, 1.35 to 15.19, 3.07 to 11.56 and 2.04 to 8.29 and interassay %CV was 0.96 to 17.40, 3.68 to 17.03, 3.94 to 17.12 and 4.87 to 16.55. Limits of quantitation range from 0.002 to 0.5 and limits of detection from 0.0008 to 0.06 mg/L. There was no significant interference from ion suppression or isobaric compounds and very little carryover. Dilution 1:2, 1:5 and 1:10 with vitreous humor gave acceptable results. Comparison of screening results from 129 post-mortem cases showed that most compounds detected in blood and/or urine were also detected in vitreous humor. Compounds more readily detected in vitreous humor included 6-monoacetylmorphine, cocaine, codeine, dihydrocodeine, olanzapine, desmethylzopiclone, diazepam, cocaethylene and desmethylmirtazapine. Compounds more readily identified in blood and/or urine included desmethylsertraline, EDDP, nordiazepam, papaverine, paracetamol and morphine. The assay is suitable for screening and quantitation of drugs and their metabolites in vitreous humor and can be used where blood and urine are unavailable, or where the analysis of vitreous humor may provide useful information.
期刊介绍：
The Journal of Analytical Toxicology (JAT) is an international toxicology journal devoted to the timely dissemination of scientific communications concerning potentially toxic substances and drug identification, isolation, and quantitation.
Since its inception in 1977, the Journal of Analytical Toxicology has striven to present state-of-the-art techniques used in toxicology labs. The peer-review process provided by the distinguished members of the Editorial Advisory Board ensures the high-quality and integrity of articles published in the Journal of Analytical Toxicology. Timely presentation of the latest toxicology developments is ensured through Technical Notes, Case Reports, and Letters to the Editor.
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