Identification and quantification of mepirapim and acetyl fentanyl in authentic human whole blood and urine samples by GC–MS/MS and LC–MS/MS

Abstract

PurposeWe encountered a curious case in which two male subjects self-administered mepirapim plus acetyl fentanyl by different routes, i.e., intravenously and by inhalation. We have thus established a detailed procedure for quantification of mepirapim and acetyl fentanyl in whole blood and urine specimens using gas chromatography (GC)–tandem mass spectrometry (MS/MS).MethodsThe GC–MS/MS method was validated for linearity, extraction recovery, accuracy, and precision. Liquid chromatography–MS/MS was also used for identification of the target compounds.ResultsGood linearity and reproducibility were achieved in the range of 20–1000 ng/g for both target compounds in both matrices. The concentrations of mepirapim in heart whole blood, femoral vein whole blood, and urine of the deceased individual with administration by intravenous injection were 593, 567, and 527 ng/g, respectively; those of acetyl fentanyl were 155, 125, and 126 ng/g, respectively. The mepirapim and acetyl fentanyl concentrations in the urine specimen of the surviving individual who had administered them by inhalation were 4900 and 570 ng/g, respectively.ConclusionsTo our knowledge, with the exception of a brief mention of a mepirapim concentration in a serum sample in emergency medicine, there are no reported data on the identification and quantification of mepirapim in biological samples. Mepirapim is a new synthetic cannabinoid. The concentration profiles of unchanged mepirapim in whole blood and urine were quite different and unique. A detailed clarification of such uniqueness is under way in our laboratory.

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

“…The concentrations of mepirapim (554-587 ng/ mL) and acetyl fentanyl (170-212 ng/mL) in blood samples were similar to those of our previous study using the usual IS calibration method (mepirapim, 563-593 ng/mL and acetyl fentanyl, 125-155 ng/mL) [4]. As described in our previous report, the concentrations of mepirapim in blood specimens were much higher than those of various other synthetic cannabinoids (0.1-199 ng/mL) in previous reports of poisoning deaths [2,[18][19][20].…”

“…The urinary level of unchanged mepirapim in the deceased individual was also as high as 309 ng/mL, although the concentration was slightly lower than that previously found (527 ng/mL) [4]. In addition, our previous study showed that the urine concentration of unchanged mepirapim in a surviving individual was much higher than expected (4900 ng/mL) [4]. Such a high concentration has never been observed for other synthetic cannabinoids; the levels of unchanged synthetic cannabinoids in human urine specimens are generally very low at subnanograms/mL [21].…”

“…On the other hand, the concentrations of acetyl fentanyl in the femoral vein and heart whole blood were at levels relatively similar to those of previous reports; the acetyl fentanyl blood levels in fatal cases were 6-600 ng/mL [10], 250-260 ng/mL [11], 153 ng/mL [12], 270 ng/mL [13], 192-285 ng/mL [14] and 235 ng/mL [15]. The urinary level of unchanged mepirapim in the deceased individual was also as high as 309 ng/mL, although the concentration was slightly lower than that previously found (527 ng/mL) [4]. In addition, our previous study showed that the urine concentration of unchanged mepirapim in a surviving individual was much higher than expected (4900 ng/mL) [4].…”

“…All specimens were stored at − 80 °C until analysis. The 'Angela' drug product found at the scene was seized and analyzed; the powder consisted of 73.2 ± 0.4% mepirapim and 18.9 ± 0.2% acetyl fentanyl (w/w) [4]. Drug analyses from the deceased were performed at our department by the request of judicial authorities.…”

“…We previously encountered a curious case in which two male subjects self-dosed mepirapim plus acetyl fentanyl by different routes of administration, that is, intravenously and by inhalation [4]. Mepirapim is a new and unique synthetic cannabinoid that was first identified in herbal blends in Japan [5].…”