Comparison of the Detection Windows of Heroin Metabolites in Human Urine Using Online SPE and LC–MS/MS: Importance of Morphine-3-Glucuronide

Heroin abuse is a serious problem that endangers human health and affects social stability. Though often being used as confirmation of heroin use, 6-monoacetylmorphine (6-MAM) has limitations due to its short detection window. To compare the detection windows of heroin metabolites (morphine (MOR), 6-MAM, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G)) in human urine, an automated online solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and fully validated. The limits of detections (LODs) of the four metabolites were in the range of 1.25-5 ng/mL. Intra and inter-day precision for all the metabolites was 0.4-6.7% and 1.8-7.3%, respectively. Accuracy ranged from 92.9 to 101.7%. This method was then applied to the analysis of urine samples of 20 male heroin abusers. M3G was detected 9-11 days after admission to the drug rehabilitation institute in 40% of heroin users while MOR or M6G was not always detected. The detection window of M3G was thus the longest. Furthermore, M3G had a much higher concentration than MOR and M6G. Therefore, M3G could provide diagnostic information with regard to heroin exposure in the combination with other clues (e.g., heroin seizures at the scene).