Interpretation of hair analysis for fentanyl and analogues

Abstract

Nowadays, the detection of new psychoactive substances (NPS) in hair has been extensively described. Although most NPS fall into the classes of synthetic cannabinoids and designer cathinones, novel synthetic opioids (NSO) have also appeared recently on the drug market with a progressive increase in their consumption. In turn, also the detection of NSO in hair has already been presented [1] , but their results interpretation still presents several controversial issues, as is quite common in hair analysis. Lack of knowledge about both effective dosage of NSO and their keratin binding make any attempt to establish a reasonable cut-off value for each drug questionable. In this presentation, preliminary results from a large dataset of real samples positive to fentanyl or analogues will be discussed. A simple, fast, specific and sensitive UHPLC-MS/MS method able to detect 13 synthetic opioids (including fentanyl analogues) and metabolites in 25 mg of hair was applied to 293 real samples. LOD values were in the range 0.1–0.3 pg/mg for all analytes, with the exception of oxycodone which was 1.5 pg/mg. Samples were collected in the United States between November 2016 and August 2018 from subjects who had reported heroin use in the last year or had already tested positive to common opiates. The range of concentrations, mean and median were calculated for each analyte. In particular, 68% of samples resulted positive for fentanyl at concentrations between LOQ and 8600 pg/mg. The mean value was 382 pg/mg and the median was 95 pg/mg. Furthermore, the metabolites norfentanyl and 4-ANPP were also monitored. Ranges of values lied between LOQ and 320 pg/mg and between 1 and 1400 pg/mg, respectively. The ratio norfentanyl/fentanyl, 4-ANPP/fentanyl and norfentanyl/4-ANPP were also evaluated. Fentanyl and analogues were measured in a wide range of concentrations. Median and box-plot calculations were used to draw a preliminary direction for a possible cut-off to discriminate between exposure to either low or high quantities of the drug. The main metabolites could also be detected in the majority of hair samples, thus the active use could be confirmed. Finally, several ratios proved promising as possible markers of active use and to discriminate the intake of fentanyl from other analogues. Like other classes of NPS, more data about the detection of NSO in hair are needed before any clear interpretation of analytical findings can be given. However, our preliminary results provide a useful starting point for a wide discussion aimed to a better understanding of fentanyl (and analogues) positive testing from hair analysis.