Norcarfentanil: carfentanil misuse or remifentanil treatment?

Abstract

Purpose Since the early 2010s, deaths due to the use of new synthetic opioids (NSO) including fentanyl and its analogs have been increasing dramatically. As fentanyl analogs bear strong structural similarities, they can share common metabolites. In some clinical or forensic cases, it can be important to demonstrate the presence of both the metabolite and the parent product to confirm that the compound is responsible for the intoxication. Norcarfentanil is a common metabolite of carfentanil (NSO) and remifentanil (widely used in medical care). This article reported the investigation of norcarfentanil origin in three cases. Methods Comprehensive screenings were performed using gas chromatography coupled to mass spectrometry and liquid chromatography coupled to a diode array detection, whereas targeted screening of NSO were performed using liquid chromatography coupled to tandem mass spectrometry. Results Norcarfentanil was detected at concentrations ranging from 0.05 to 15.8 ng/mL in plasma and from 8.8 to 1820 ng/ mL in urine, but carfentanil was detected in two out of the three cases. The presence of norcarfentanil has been supposed to be due to the treatment with remifentanil during the medical care of the patient. Conclusions In the first two cases, norcarfentanil was present as the metabolite of carfentanil, whereas in the last case, norcarfentanil was the metabolite of remifentanil. Without the identification of remifentanil, confusion could occur, and norcarfentanil could be attributed to carfentanil misuse.

Development and application of a High-Resolution mass spectrometry method for the detection of fentanyl analogs in urine and serum

“…Carfentanil, the most potent analog known to date, was found to have an LOD of 1 ng/mL in urine and 0.25 ng/mL in serum. In case studies, carfentanil concentrations were found to be 0.03–12 ng/ml in urine and 0.1–120 ng/mL in blood [27] . Therefore, given the limited information available for fentanyl analog pharmacokinetics, the FAS method is expected to provide adequate sensitivity to detect most, if not all, fentanyl analogs at physiologically relevant concentrations in clinical cases.…”

In Vitro and In Vivo Analysis of Fentanyl and Fentalog Metabolites using Hyphenated Chromatographic Techniques: A Review

“…METABOLITES Fentanyl and fentalogs have very similar structures indicating that their metabolites could be common. 44 Understanding the metabolism and detection of the metabolite of a drug is the first lead in the detection of any drug in forensic toxicology casework. In cases of drug intoxication or overdose, the detection of drug metabolites in biological specimens can help to determine the cause of death and the lethal dosages of a particular drug.…”

“…A prior detection of remifentanil is required to confirm the drug. 44 Kong and Walz have studied the metabolism of carfentanil not only in human lung microsomes but also in rat and dog lung microsomes. The carfentanil metabolites formed in these incubated cells were detected using ultrahigh-performance liquid chromatography−orbitrap fusion mass spectrometry (UHPLC-Orbitrap Fusion MS).…”

Development and validation of liquid chromatography‐tandem mass spectrometry targeted screening of 16 fentanyl analogs and U‐47700 in hair: Application to 137 authentic samples

“…Most are based on solid phase extraction (SPE) or liquid–liquid extraction (LLE) followed by a LC–MS/MS experiment. However, these techniques have some drawbacks: they are limited by the unavailability of reference standards (RS), 11–15 and the enrichment of the library database by the addition of new multi reaction monitoring (MRM) transitions of new compounds often requires further method optimization. Moreover, targeted screening does not allow retrospective processing of MS data to identify unknown compounds.…”