Evaluation of the long-term stability of select phenylacetylindole, cycloalkylindole, quinolinyl, and carboxamide synthetic cannabinoids using LC–MS-MS

Abstract Forensic toxicology laboratories often encounter casework backlogs, which raise concerns for drug stability that can be affected by long storage times, temperature and preservatives, or the lack thereof. The focus of this research was to evaluate the impact of these factors on the stability of 17 synthetic cannabinoids (SCs) in human whole blood and 10 associated metabolites in human urine. The fortified biological specimens were stored under room temperature (20°C), refrigerator (4°C) and freezer (–20°C) conditions for a period of 52 weeks. Preservatives included potassium oxalate, sodium ethylenediaminetetraacetic acid and sodium fluoride. Extraction of analytes was conducted using supported liquid extraction and analyzed using a liquid chromatograph-tandem mass spectrometer. Under all three storage conditions, the majority of urine metabolites were stable up to 9 weeks. All analytes in frozen sodium fluoride–preserved blood were stable at 21–52 weeks with the exception of APP-PICA. Analytes in the blood that were stable up to 52 weeks in the freezer generally had a core structure of a carbonyl substituent on a pyrazole or pyrrole with surrounding nonpolar groups. In contrast, compounds with two adjacent polar carbonyl functional groups experienced degradation at ≤1 week under ambient temperature and refrigeration. 5-Fluoropentyl analogs, XLR11 and 5-fluoro ADB-PINACA, in comparison to their counterpart analytes, UR144 and ADB-PINACA, were unstable at earlier time points under all temperatures. Based on these data, forensic blood evidence suggesting the presence of SC compounds is recommended to be frozen with sodium fluoride and potassium oxalate preservatives for optimal quantitative results.