Evaluation of screening results of an untargeted metabolite-based LC-MS/MS screening for vitreous humor

In case of standard biological postmortem matrices such as blood or urine being unavailable, vitreous humor has been shown to be a versatile matrix used as alternative for postmortem systematic toxicological analysis for the detection of drugs and their metabolites. This study focused on the qualitative detection of drugs in vitreous humor using an untargeted metabolite based LC-M/MS screening approach. Vitreous humor samples were retrospectively analyzed by LC-MS/MS after being worked-up by protein precipitation. In n = 96 samples 418 detections were recorded. Those corresponded to 121 different xenobiotics. Cardiovascular drugs being the most frequently detected drug class followed by (local) anesthetics, neuroleptics, and antidepressants. Drug exposure was indicated 227 times (∼ 54 %) solely by the presence of the parent compound. One hundred thirty seven times (∼ 32 %) a parent compound and corresponding metabolite(s) were detected. Fifty four times (∼ 13 %) a drug exposure was indicated solely by the detection of metabolites. Out of those 54 detections, 32 times corresponding metabolites were not common commercially available. Therefore, the authors suggest that metabolite information should be considered for a vitreous humor based screening approach. Screening for metabolites will lead to ∼13 % more detections, if the corresponding metabolites are covered by the applied screening approach. The obtained results pointed out, that some compounds are exclusively found in form of their corresponding phase II metabolites. No linkage between protein binding or molecular weight was found for the detection of a compound in vitreous humor either by parent compound or metabolite(s).