Detection of Non-Prescription Heroin Markers in Urine with Liquid Chromatography--Atmospheric Pressure Chemical Ionization Mass Spectrometry

Abstract

The planned introduction of a prescription heroin program in Germany created a need for differentiation between non-prescription and prescribed diamorphine use. The following substances were chosen as markers of non-prescription heroin: acetylcodeine (AC); its metabolites codeine (C) and codeine 6-glucuronide (C6G); papaverine (P); and noscapine (N). Typical heroin markers diamorphine (DAM) and its metabolites monoacetylmorphine (MAM) and morphine (M) were also determined. The drugs were extracted from urine samples with solid-phase extraction (C18) using standard 200-mg columns and 96-well microplates (100 mg). The extracts were examined with liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (positive ionization) in two isocratic systems. Selected ion monitoring procedures were applied for protonated molecular masses and characteristic fragments of drugs involved. The limits of detection were in the range of 0.5-1 ng/mL urine. The occurrence of selected heroin markers was investigated in 25 urine samples collected from heroin abusers (road traffic offenders and overdosed patients). C6G was found in all samples, C in 24 samples, N in 22 samples, MAM in 16 samples, P in 14 samples, DAM in 12 samples, and AC in 4 samples. The appearance of these compounds in urine reflects their pharmacokinetic properties and the composition of non-prescription heroin.

GC-MS detection and characterization of thebaine as a urinary marker of opium use

“…Any of the nonpsychoactive opium alkaloids shown in Table 1 [4][5][6][7][8][9][10][11] is a potential marker of opium use if it is detected in urine together with morphine and codeine. However, because some of these alkaloids have sources other than opium (Table 1), the unequivocal confi rmation of opium use requires the detection of as many alkaloids as possible for a test sample.…”

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

“…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].…”

GC-MS detection and tentative characterization of two noscapine metabolites in human urine and their potential as markers for opium and illicit heroin use

“…It is a frequent carryover impurity in illicit heroin powder; its contents are about 10% (w/w) in the Pakistani type 1 and Iranian heroin, and only trace in Chinese, Indian, Pakistani type 2, and Turkish heroin [2]. It was also reported as a major adulterant of illicit heroin [3][4][5][6].…”

“…Noscapine [2] and its metabolites, meconin and desmethylmeconin [10], have been detected in urine and proposed as markers of illicit heroin use, in differentiation from medicinal heroin (diamorphine) use. We published some reports highlighting the use of the marker compounds, such as reticuline and neopine, for proving the illicit use of opium and opiate products [11,12].…”