Postmortem distribution of mepirapim and acetyl fentanyl in biological fluid and solid tissue specimens measured by the standard addition method

Abstract

Purpose Mepirapim is a new synthetic cannabinoid. We previously reported that the concentrations of unchanged mepirapim in whole blood and urine were much higher than those of other synthetic cannabinoids. To determine the postmortem distribution of mepirapim and acetyl fentanyl in the deceased individual, we established a standard addition method for detailed analysis by liquid chromatography-mass spectrometry (LC-MS) for quantification of these drugs. Methods The LC-MS method was fully validated for linearity, extraction recovery, matrix effect and repeatability. Results Good linearities, extraction recoveries, matrix effects and repeatabilities were shown for both target compounds in all specimens. The concentrations of mepirapim and acetyl fentanyl in three body fluid specimens and 12 solid tissue specimens were measured. For mepirapim, the highest concentrations were found in the liver and kidney, and the concentrations in the blood and urine specimens were one order of magnitude lower than the high concentrations in the solid tissues except the psoas major muscle. For acetyl fentanyl, the highest concentrations were found in the myocardium, spleen and kidney, and the concentrations in the body fluid specimens were also one order of magnitude lower than the highest concentrations in the solid tissues. There were concentration differences of mepirapim and acetyl fentanyl among the regions of the brain. Conclusions The concentration of unchanged mepirapim in urine was much higher than those of other synthetic cannabinoids; the higher dosage, urinary excretion, metabolisms and/or pharmacokinetics of mepirapim may be quite different from those of other synthetic cannabinoids.

The standard addition method and its validation in forensic toxicology

“…In recent years, it seems likely that scientific reports using SAM are increasing, but in many of them except our reports, the validation data for SAM are either missing, incomplete or confusingly mixed with the validations of MMCM [48][49][50][51][52][53][54][55] (see Table 1). Only one report [56] describing postmortem distribution of mepirapim and acetyl fentanyl in a cadaver that died of drug poisoning presented satisfactory validation data for SAM, which were similar to those proposed by our group [25, 28, 31-35, 37, 39].…”

Time- and temperature-dependent postmortem concentration changes of the (synthetic) cannabinoids JWH-210, RCS-4, as well as ∆9-tetrahydrocannabinol following pulmonary administration to pigs

“…Thus, national and international guidelines recommend the standard addition approach for quantification of drugs in PM specimens (GTFCh 2018; Jickells and Negrusz 2008;Peters et al 2007;Skopp 2010;SOFT/AAFS 2006). Following this recommendation, this procedure has frequently been applied in quantitative PM studies on the tissue distribution of drugs (Hasegawa et al 2014;Mochizuki et al 2019;Schaefer et al 2017b;Siek and Dunn 1993). In particular in case reports of human fatalities the standard addition method has been used for PM analysis indicating that this is the prevailing analytical procedure in routine PM examination.…”

Use of Diagnostic Ions for the Detection of Fentanyl Analogs in Human Matrices by LC–QTOF

“…The LRL 100 values range from 0.25 to 5 ng/mL with no discernible trend between the LRL 100 values in urine and plasma. Reported concentrations of fentanyl and fentanyl analogs following exposure have varied greatly, with reported fentanyl, carfentanil, acetylfentanyl, and furanylfentanyl concentrations ranging from 0.0102 to 827 ng/mL in human matrices. − Although sensitivity may preclude the detection of all exposures due to delayed sample collection or opioid toxicity, the LRL values of the eight chosen fentanyl analogs suggest that this method has the capability to detect fentanyl-related compounds in true exposure samples. Ultimately, however, the absence of any analyte cannot be definitively reported without characterization of the individual compound’s LRL 100 .…”