Urinary Excretion of Codeine and Morphine following the Administration of Codeine-Containing Cold Syrup

Journal of Analytical Toxicology, Mar 2000

The concentrations of codeine ([C]) and morphine ([M]) excreted in urine obtained from nine subjects at various time intervals after the ingestion of 10–40 mg of both simple and compound codeine doses three times per day for three days were determined by gas chromatography-mass spectrometry analysis. Four distinct [C]/[M] distribution patterns (phases) were observed: a, [C] > [M] from ingestion of first dose to 78–108 h after ingestion of the first dose (18–48 h after the ingestion of the last dose); b, [C] ≈ [M] 78–90 h after ingestion of the first dose (18–30 h after ingestion of the last dose); c, [C] < [M] 78–102 h after ingestion of first dose (18–42 h after ingestion of the last dose); and d, [C] < 0.05 µg/mL and [M] > 0.05 µg/mL 84–96 h after ingestion of the first dose (24–36 h after ingestion of the last dose with [M] ranging from 0.10 to 0.30 µg/mL) toward the terminal phase. No single individual exhibited all four [C]/[M] distribution characteristics during the entire excretion period and intervals monitored in this study. These data are of reference value for differentiating codeine and morphine/heroin ingestion.

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Urinary Excretion of Codeine and Morphine following the Administration of Codeine-Containing Cold Syrup

Journal of Analytical Toxicology Urinary Excretionof Codeineand Morphine following the Administrationof Codeine-ContainingCold Syrup Ber-tin Chang 0 M i n - K u n Huang 0 0 Division of Drug Chemistry, National Laboratoriesof Foodsand Drugs , Departmentof Health, ExecutiveYuan, 161-2 Kuen YangStreet,Nankong, Taipei , Taiwan The concentrationsof codeine ([C]) and morphine ([M]) excreted in urine obtained from nine subjectsat varioustime intervalsafter the ingestionof 10-40 mg of both simple and compound codeine dosesthree times per day for three days were determined by gas chromatography-massspectrometry analysis.Four distinct [C]/[M] distribution patterns(phases)were observed:a, [C] > [M] from ingestionof first doseto 78-108 h after ingestionof the first dose (18-48 h after the ingestionof the last dose);b, [C] ~ [M] 78-90 h after ingestionof the first dose (18-30 h after ingestionof the last dose); c, [C] < [M] 78-102 h after ingestionof first dose (18-42 h after ingestionof the last dose); and d, [C] < 0.05 pg/mL and [M] > 0.05 pg/mL 84-96 h after ingestionof the first dose (24-36 h after ingestionof the lastdose with [M] rangingfrom 0.10 to 0.30 pg/mL) toward the terminal phase.No single individual exhibited all four [C]/[M] distribution characteristics during the entire excretion period and intervalsmonitored in this study.Thesedata are of reference value for differentiating codeine and morphine/heroin ingestion. Introduction Ingestion of cold syrup containing codeine has frequently been reported (or claimed) to be the cause of positive morphine urine test results. This study, in which urinary excretion of morphine and codeine were monitored followingthe ingestion of opiate-containing materials, was conducted to add data to the literature base ( 1-7 ). In this study, ingestion patterns similar to those followedfor therapeutical purposes were adopted with the hope that information generated by this study may be of reference value to help characterize codeine/morphine excretion patterns following the ingestion of codeine-containing cold syrup, which is currently a popular cold remedy in Taiwan. Materials and M e t h o d s Chemicals and reagents Drug-free urine (blank urine) was purchased from Bio-Rad (Anaheim, CA).Nalorphine was purchased from Sigma Chemical (St. Louis, MO),and morphine and codeine solutions (1.0 mg/mL in methanol) were purchased from Radian International (Austin, TX). N-Methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) was purchased from Aldrich Chemical (Milwaukee, WI). Trishydroxymethylaminomethane was purchased from Riedel-deHaen A G (Seelze, Germany). "Simple" and "compound" codeine syrup were prepared inhouse as described. Simple codeine syrup contained 1 mg codeine phosphate in each milliliter, and each milliliter of compound codeine syrup contained 2 mg of codeine phosphate, 2.5 mg of pseudoephedrine hydrochloride, and 0.4 mg of chlorpheniramine maleate. Codeine intake and urine collection The nature and purpose of this study were fully explained to the nine healthy male volunteers recruited for this study. They were instructed not to take any medicines for two weeks prior to the intake of the first dose. These nine volunteers were evenly divided into three groups that received 10-, 20-, and 40rag codeine doses (simple codeine syrup), respectively. One dose was taken following each meal (three times per day) for three days, daytime only. Urine was collected at 0, 1, 2, 4, and 6 h, then at every 6 (+ 1) h, until both codeine and morphine became undetectable (< 0.05 lJg/mL). Urine samples were collected in bottles, capped, and stored at -20~ until analysis. Two weeks after the completion of the first experiment, another nine volunteers were again randomly divided into three groups of equal size, following the same intake practice, to receive 10-, 20-, and 40-rag codeine doses (compound codeine syrup), respectively. Analytical procedures Urine samples were first screened for opiates using TDXanalyzer and TDx reagents provided by Abbott Laboratories (Abbott Park, IL). The test procedure provided by the manufacturer was followed. The lowest concentration that can be distinguished from zero with 95% confidence was 0.05 IJg/mL. Samples that were tested above 0.1 l~g/mLwere proceeded to pretreatment and gas chromtography-mass spectrometry Reproduction (photocopying) of editorial content of this journal is prohibited without publisher's permission. Downloaded from https://academic.oup.com/jat/article-abstract/24/2/133/853734 by guest on 10 June 2018 (GC-MS) protocols, in which qualitative and quantitative analysis for codeine and morphine were performed. Urine samples (4 mL) incorporating 5.00 IJg/mL internal standard (nalorphine) were then acid hydrolyzed in a screwcapped Pyrex glass tube with 0.5 mL 37% HCI at 121~ for 15 min. Solid-phase extraction (SPE) was performed using Chem Screen Cadan 203 SPE cartridges purchased from United Chemical Technology (Bristol, PA), fol (...truncated)


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Chang, Ber-Lin, Huang, Min-Kun. Urinary Excretion of Codeine and Morphine following the Administration of Codeine-Containing Cold Syrup, Journal of Analytical Toxicology, 2000, pp. 133-139, Volume 24, Issue 2, DOI: 10.1093/jat/24.2.133