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
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(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)