Detection of Acetylcodeine in Urine as an Indicator of Illicit Heroin Use: Method Validation and Results of a Pilot Study

BACKGROUND: Acetylcodeine (AC), an impurity of illicit heroin synthesis, has been suggested as an interesting biomarker of illicit heroin use. METHODS: Procedures were developed for quantification of (a) morphine, 6-monoacetylmorphine (6-AM), and codeine in urine and (b) diacetylmorphine and AC in urine. Solid-phase extraction of the analytes was performed, and the extracted analytes were analyzed by selected-ion monitoring with gas chromatography-mass spectrometry. This procedure required prior derivatization with propionic anhydride. RESULTS: Different validation parameters were determined, such as linearity, reproducibility, extraction recoveries, and cutoffs. Seventy-one urine specimens of illicit heroin abusers and 44 urine specimens of subjects in a heroin maintenance program were analyzed. AC was detected in 85.9% of the samples of the first group but not in any of the samples from subjects taking medical heroin. In the two groups, there were 94.4% and 84.1% 6-AM positive urine specimens, respectively. Detection times were determined for AC and codeine by parallel administration of heroin containing various percentages of AC to four voluntary patients in a heroin maintenance program. The measured detection times were 8 and 23 h for AC and codeine, respectively. CONCLUSIONS: These results indicate that, together with detection of 6-AM in urine, AC is a suitable marker of illicit heroin use.