Urinary antimony as a biomarker for differentiating heroin and Brown mixture use

Heroin is classified as a Schedule I controlled substance with severe legal consequences for its use, whereas liquid Brown Mixture (BM) is a legally available and commonly prescribed cough remedy in Taiwan. However, numerous cases of BM ingestion have been misinterpreted as heroin use because BM contains opium tincture, leading to similar urine test results. Owing to the rapid metabolism of heroin, detection of the parent drug and its primary metabolite, 6-acetylmorphine, in urine is difficult; thus, interpretation often relies on morphine concentration and the morphine-to-codeine (M/C) ratio, which can be inconclusive. In our BM analysis, the M/C ratio was 3.3 ± 0.4, and among 5094 morphine-positive urine samples, 279 (5.5%) had M/C ratios between 2 and 4, suggesting that a substantial number of individuals could be misidentified. Given the lack of reliable urinary biomarkers to distinguish BM from heroin use, this study aimed to identify BM-specific indicators. BM contains antimony (Sb) potassium tartrate, an emetic agent absent in heroin formulations. Although urinary Sb levels are low, they can be quantified using highly sensitive inductively coupled plasma mass spectrometry (ICP-MS). A pharmacokinetic study involving single and multiple BM doses revealed that urinary Sb increased from ≤0.11 ng/mL pre-dose to 0.4-98.9 ng/mL post-dose. Morphine and codeine were determined using gas chromatography-mass spectrometry (GC-MS), and M/C ratios ranged from 2.0 to 14.9, showing a secondary rise at later stages. These findings suggest that urinary Sb may serve as a useful supplementary biomarker for BM ingestion, thereby enhancing the accuracy of forensic toxicological interpretation and reducing false identification of heroin use.