Acetylcodeine as a Urinary Marker to Differentiate the Use of Street Heroin and Pharmaceutical Heroin

Abstract

Acetylcodeine (ACOD) is a synthesis byproduct present in street heroin but not in pharmaceutical diacetylmorphine (DAM) as used in the Swiss program Heroin-Assisted Treatment for Opiate Dependent Drug Users (HAT). ACOD was evaluated and validated as an urine marker to detect the consumption of street heroin by HAT participants. A gas chromatography-mass spectrometry method allowing the quantitation of ACOD concentrations as low as 0.2 ng/mL urine has been developed. In opiate-naïve subjects, intravenous (i.v.) ACOD showed a plasma elimination half-life of 237 +/- 18 min, urine peak concentrations 2 h after administration, and a detection window of 8 h. Only 0.4 +/- 0.1% was excreted unchanged, with codeine (COD) as the main metabolite. ACOD may be formed by transacetylation when i.v. DAM and oral codeine are co-administered. To avoid false-positive results, the calculation of COD/ACOD ratios is recommended. In a study with 105 HAT participants, 14% of the tested urines were ACOD positive. Only a low correlation was found between the anonymously self-declared consumption of street heroin and the ACOD positive rate.

Comparison of urine results concerning co-consumption of illicit heroin and other drugs in heroin and methadone maintenance programs

“…In other HER-assisted treatment settings, AC was tested positive in 14-32% in urine samples of patients [5,7] which is also comparable to our results. However, in the present study, a co-consumption of illicit HER in the HMP was determined with 50% but was significantly lower compared to the MMP with a co-use of 71%.…”

“…The LC-MS/MS procedure used in the present study permitted the simultaneous determination of nine substances which are considered as general markers of heroin use or rather as specific markers of illicit heroin abuse [2,[4][5][6]. The procedure is useful for the analytical differentiation between prescribed pharmaceutical heroin use and illicit heroin abuse on the basis of urine analysis.…”

“…Codeine (COD) was most frequently detected as an additional marker substance in urine of illicit heroin users, but only its acetylated form, acetylcodeine (AC), was considered as a definite biomarker [2]. Otherwise, AC was found in fewer specimens and in lower concentrations than 6AM [3,4], and due to a short half-life of approximately 237 min [5], it was not detectable in urine for as long as morphine following heroin abuse [5,6]. Therefore, it was concluded that the detection of urinary metabolites of the opiate alkaloids noscapine (NOS) and papaverine (PAP) is useful for an analytical differentiation between the use of illicit heroin and pharmaceutical diacetylmorphine, which is free from further substances [7,8].…”

Screening for drugs of abuse: which matrix, oral fluid or urine?

“…Hence, attention has been directed at measuring biomarkers that may uniquely determine the use of illicit heroin including noscapine, papaverine and their metabolites 95 and 6-acetylcodeine. 96 As expected, most published work with respect to these markers has been conducted on urine. Acetylcodeine measurements have been done on both oral fluid 51 and urine 96 in subjects using heroin.…”

“…96 As expected, most published work with respect to these markers has been conducted on urine. Acetylcodeine measurements have been done on both oral fluid 51 and urine 96 in subjects using heroin. The variability of acetylcodeine concentrations in illicit heroin does pose problems with the sensitivity of this investigation in detecting street heroin use.…”