Simultaneous quantitative analysis of epimeric and Δ8/Δ9 positional isomers of synthetic THC analogs and natural cannabinoids in formulated products by UHPLC-DAD with optional ESI/TOFMS confirmation

The 2018 U.S. Farm Bill legalized hemp but created regulatory gaps that contributed to the emergence of synthetic THC analogs in consumer products. An UHPLC-DAD method was developed and validated in accordance with ISO/IEC 17025 guidelines for the quantitative analysis of twenty-three neutral cannabinoids, including two epimeric pairs and six Δ8/Δ9 positional isomer pairs of synthetic THC analogs, six naturally occurring neutral cannabinoids, and one common synthetic THC byproduct. The method was applied to fifteen commercial products comprising four tinctures, six vaping oils, and five gummies. Fourteen cannabinoids were detected above their limits of quantification at concentrations ranging from 0.008–79.6%, with triplicate relative standard deviations of 0.8–18.3%. Analytical results revealed mislabeling in ten of the fifteen samples. Real-time recovery was evaluated using spiked abnormal CBD, a synthetic cannabinoid structurally unrelated to the target analytes, yielding recoveries of 95.0–110.3% with RSDs of 1.0–10.5% across all matrices. High-resolution ESI/TOFMS was used for optional confirmation, verifying method specificity, minimal matrix interference, and the presence of several HHC stereoisomers.