Urinary Excretion of Morphine and Codeine Following the Administration of Single and Multiple Doses of Opium Preparations Prescribed in Taiwan as "Brown Mixture"by H.-C. Liu, H.-O. Ho, R. H. Liu, G.-C. Yeh, D.-L. Lin

Journal of Analytical Toxicology

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Journal of Analytical Toxicology, Vol. 30, May 2006

Urinary Excretion of Morphine and Codeine

Following the Administration of Single and

Multiple Doses of Opium Preparations

Prescribed in Taiwan as "Brown Mixture"

Hsiu-Chuan Liul, 2, Hsiu-O Ho 2, Ray H. Liu 3, Geng-Cheng Yeh 4, and Dong-tiang Linl,S, * 1Department of Forensic Toxicology, Institute of Forensic Medicine, Ministry of Justice, Taipei, Taiwan; 2Graduate Institute of Pharmaceutical Sciences, Taipei Medical University, Taipei, Taiwan; 3Department of Medical Technology,

Fooyin University, Kaohsiung Hsien, Taiwan; 4Department of Pediatrics, Taipei Medical University, Taipei, Taiwan; and

SDepartment of Medical Technology, Taipei Medical University, Taipei, Taiwan.

Abstract Introduction

Parallel to the "poppy-seed defense" strategy commonly reported in the United States, donors of urine samples tested positive for opiates in Taiwan often claimed the consumption of

Brown Mixture (BM) as the source of the observed morphine and codeine. Because BM contains opium powder (10.0-10.5% morphine), opium tincture (0.9-1.1% morphine), or camphorated opium tincture (0.045-0.055 % morphine) and is a popular remedy, and heroin use is considered a serious criminal act, the claim of BM use has to be adequately addressed. In this study, 8M from seven different manufacturers (5 tablets and 2 solutions) and urine samples from alleged heroin users and volunteers with various ingestion patterns and were analyzed for their morphine and codeine contents. The analytical procedure included hydrolysis, trimethylsUylation, andgas chromatography-mass spectrometry analysis. The contents of morphine and codeine in the tablets were found to be very consislenl, but with significant differences in the wo BM solutions.

Morphine concentrations found in urine specimens collected from volunteers ingesting BM tablets (orsolutions) were always < 4000 ng/mL. ]'he following morphine-to-codeine ([M]/[C]) ratios were observed for urine specimens with morphine concentration > 300 ng/mL: (A) < 3.0 for volunteers ingesting BM solution and (B) > 3.0 (mostly > 5.0) for volunteers ingesting BM tablets and alleged heroin users. It appeared that (A) BM ingestion (tablet or solution) was unlikely to result in a morphine concentration > 4000 ng/mL; and (B) [M]/[C] ratio might not be an effective parameter to differentiate heroin use from BM tablet ingestion. * Author to whom correspondence should be addressed: Dr. Dong-Liang Lin, Chief

Toxicologist, Institute ofForensic Medicine, Ministry of Justice, No. 16, Lane "~ 75,

Tong-Hwa Street, Taipei 106, Taiwan. E-maih dllin@mail.moj.gov.tw.

Parallel to the "poppy-seed defense" strategy (1-3) commonly reported in the United States, donors of urine samples tested positive for opiates in Taiwan often claimed the consumption of Brown Mixture (BM) I as the source of the observed morphine and codeine. Because BM contains opium powder (10.0-t0.5% morphine) (4), opium tincture (0.9-1.1% morphine) (4), or camphorated opium tincture (0.045-0.055% morphine) (4) and is a popular cold remedy, and heroin use is considered a serious criminal act in Taiwan, the claim of BM use has to be adequately addressed. Although the presence of 6-monoacetylmorphine is an indication of heroin exposure (1), the half-life of this heroin metabotite is relatively short (5); thus, the presence/absence of this metabolite may not always be an effective criterion for differentiating samples derived from heroin users from those ingesting other opiates-containing materials.

With this in mind, the authors conducted a study to investigate the characteristics ofurine samples collected from volunteers who have received oral doses of BM. The morphine-tocodeine ([M]/[C]) ratio and their concentration levels in these samples were compared with those from alleged heroin abuse cases. It was hoped that these parameters (6) might help confirm non-heroin use. In this study, BM from seven different manufacturers (5 tablets and 2 solutions--all that are available in Taiwan) and urine samples from volunteers and alleged heroin users were analyzed for their morphine and codeine contents.

I Brown Mixture is a legal prescription drug in Taiwan. Each tablet contains 2.5 mg opium powder 110.0-I 0.5% morphine), 0.48 mL glycyrrhiza extract, 1.0 mg antimony potassium tartrate, 2.5 mg benzoic acid, 1.5 mg camphor, 0.001S ml_ anise oil, and lactose.

Reproduction (photocopying) of editorial content of this journal is prohibited without publisher's permission. 225

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Materials and Methods

Chemicals and reagents

All solvents and reagents were high-performance liquid chromatography grade and purchased from J.T.Baker Chemical Corporation (Phillipsburg, N J). N-Methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) was obtained from Sigma

Aldrich Chemical Corporation (Milwaukee, WI). Codeine, morphine, and nalorphine solutions (1.0 mg/mL in methanol) were provided by Cerilliant Corporation (Austin, TX). Urine confirmed negative by GC-MS was used toprepare standards and controls.