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The present study describes the simultaneous determination of four drugs, two local anaesthetics (lidocaine and bupivacaine) and two opium alkaloids (noscapine and papaverine) by capillary zone electrophoresis (CZE) with solid-phase extraction (SPE) procedure using Oasis HLB cartridges. Their recoveries ranged from 81 to 107% at the target concentrations of 2.0, 5.0 and 8.0 microgmL(-1) in spiked urine samples. Coefficients of variation of the recoveries ranged from 2.1 to 11.3% at these concentrations. The quantitation limits of the method were approximately 300 ngmL(-1) for the different compounds studied. The assay is very specific for these compounds and requires a short sample preparation procedure prior to the electrophoretic analysis.

In this study the use of the various opiate alkaloid contaminants as potential markers for illicit heroin ingestion were investigated. Urine samples (n = 227) taken from prisoners for routine drug screen, which were positive for opiates by immunoassay screening, were analyzed for contaminants in illicit heroin. A previously described method was used for the analysis; urines were extracted using mixed-mode solid-phase extraction; the extracts were derivatized using N-methyl-bistrifluoroacetamide and N-methyl-N-trimethylsilyltrifluoroactamide/trimethylchlorosilane. The derivatized extracts were subjected to electron impact gas chromatography-mass spectrometry. The extracts were injected in full scan mode followed by selected ion monitoring mode for target opiate alkaloids found as contaminants in illicit heroin. The opiate alkaloids and their metabolites specifically targeted included meconine, desmethylmeconine, hydrocotarnine, acetylcodeine, codeine, morphine, 6-monacetylmorphine (6-mam), papaverine, hydroxypapaverine, and dihydroxypapaverine. Of the 227 samples positive for opiates by immunoassay, using a cut-off of 300 ng/mL, 199 were confirmed positive for morphine and using a cut-off of 10 ng/mL, 28 were confirmed positive for 6-mam. Using the screening method described in the study, the following numbers of positives were found: 199 for morphine, 103 for codeine, 5 for meconine, 46 for desmethylmeconine, 18 for 6-mam, 136 for hydroxypapaverine, and 139 for dihydroxypapaverine. Acetylcodeine, hydrocotarnine, and papaverine were not detected in any of the samples. The results of this study show that analysis for papaverine metabolites is more sensitive than 6-mam as a way of demonstrating illicit heroin use.

Neopine, a minor opium alkaloid and an isomer of codeine (also known as beta-codeine), has been detected in both the urine of opium users and pharmaceutical codeine users. The characterization of neopine was achieved by comparison of the mass spectra and GC retention times of the trimethylsilyl derivative. The presence of neopine in the urine of pharmaceutical codeine users was attributed to the metabolism of codeine through a double bond migration in ring C, from the 7-8 to the 8-14 position. The potential use of the alkaloid as a confirmation marker of opium and/or pharmaceutical codeine use and the ability to differentiate these from heroin use has been discussed.

Objective: To assess the reliability and validity of self-reported opium use in a rural Iranian population at high risk for esophageal cancer in preparation for a large cohort study., Method: 1,057 subjects ages 33 to 84 years were recruited from Gonbad city and three surrounding villages in Golestan province of Iran and completed a questionnaire and provided biological samples. The history and duration of using opium, smoking tobacco, chewing nass, and drinking alcohol were measured by questionnaire in the entire cohort. A subgroup of 130 people was reinterviewed after 2 months to assess reliability. Validity of the opium question was assessed by comparing the questionnaire responses with the presence of codeine and morphine in the urine of 150 selected subjects., Results: Self-reported opiate use is reliable and valid in this population. The reliability of ever opium use and duration of opium use had kappa's of 0.96 and 0.74, respectively. The validity of self-reported opium use was also high. Using urine codeine or morphine as the gold standard for use of opium, self-report had a sensitivity of 0.93 and a specificity of 0.89., Conclusions: The self-reported use of opium can provide a reliable and valid measurement in this population and will be useful for studying associations between opium use and occurrence of esophageal cancer and other diseases.

Aims: This study attempted to determine: if US federal cash disability payments increase the use of cocaine or opiates among those requalifying for supplemental security income (SSI) disability benefits compared with those who lost benefits; if drug use peaks at the beginning of the month after the receipt of the disability cash disbursement; and if money management by representative payees of requalifying SSI recipients suppresses drug use., Design: A multi-site, prospective, 2 year longitudinal design was used with follow-up interviews conducted every 6 months. Urine samples were collected at the final three follow-up interviews., Setting: Data were collected in Chicago, IL, Los Angeles, CA, and Seattle, WA, USA., Participants: This study used a randomly selected sample of 740 former recipients of SSI who had received disability benefits for drug addiction and alcoholism (DA&A) in 1996, were between the ages of 21 and 59 years, had not received concurrent social security disability insurance and provided testable urine samples and complete self-report data for at least one follow-up interview., Measurements: Independent variables included demographics, SSI status at follow-up, representative payee status, drug treatment participation and income. Time of drug testing was operationalized as the first 10 days of the month versus the last 20-21 days based on when the urine sample was collected. The dependent variables were cocaine and opiate use, determined by urinalysis results., Findings: Participants were 28% more likely to test positive for cocaine use in the first 10 days of the month than later in the month. This effect was general across all subjects and was not restricted to those receiving SSI benefits. No such effect was found for opiate use. Receiving SSI benefits did not increase cocaine or opiate use generally, nor did having a representative payee suppress use., Conclusions: The findings do not support the contentions that federal cash benefits appreciably increase drug use or that representative payees discourage use, at least when use is defined dichotomously. The 'check effect' for cocaine use appears to be general and not confined to those receiving federal cash benefits. The lack of a 'check effect' for opiate use is probably the result of the difference between a relatively steady state of opiate use associated with addiction and a binge pattern of cocaine use triggered by suddenly flush resources.

A fast liquid chromatographic method with tandem diode array-fluorescence detection for the simultaneous determination of in total 17 opium alkaloids and opioids is presented. Blank blood and urine samples (1 ml) were spiked with different concentrations of a standard mixture, as well as with the internal standard, butorphanol (2000 ng/ml). After solid-phase extraction, based on weak cation exchange (Bond Elut CBA SPE columns), the extracts were examined by HPLC-DAD-FL. By using a "high-speed" phenyl column (53 x 7.0 mm I.D., particle size 3 microm) eluted with a gradient system (A: water-methanol (90:10, v/v), B: methanol, both containing 25 mM triethylammoniumformate (pH(A) = 4.5)) all compounds could be baseline separated within 12 min. The method was validated and its applicability was demonstrated by the analysis of real-time forensic cases.

The biological material of 28 abusers of compounds from the group of opium alkaloids were toxicologically analysed. To preliminary estimation of psychoactive substances ingestion the immunoassay methods (EMIT or FPIA) were used. The received results of total estimation compounds from opium alkaloids and their metabolites were compared to the ones obtained from high-performance liquid chromatography identification method with using Remedi HS. In the evaluated materials of all patients morphine, codeine, N-desmethylcodeine were identified. The presence of 6-mono-acethylmorphine was found in the urine of only 4 patients, which indicates the instability and a little amount of heroine in "kompot" of domestic production. The identification method can be used for simultaneous estimation of other substances of abuse from the groups of amphetamines and phenothiazines.

The pharmacokinetics of the 1R cis-1'R cis-isomer of atracurium (51W89) and its metabolite, laudanosine, were studied in 11 healthy patients with normal renal function and in 12 patients with chronic renal failure undergoing regular dialysis. A bolus dose of 51W89 (0.1 mg/kg) was given, and the plasma concentration was measured at regular intervals for 480 min. The elimination half-life of 51W89 was significantly longer in renal failure patients than in healthy controls (38.9 min vs 30.6 min; P < 0.05). The plasma laudanosine levels were lower than those reported after an equipotent dose of atracurium besylate. 51W89 may have a prolonged effect in renal failure patients.

The newest formulation of the EMIT assay for drugs of abuse, EMIT II, and a new immunoassay, OnLine, using the kinetic interaction of microparticles in solution methodology, were evaluated for marijuana, cocaine, opiates, barbiturates, and phencyclidine. Both types of immunoassays were performed on an Hitachi 717 analyzer. Calibration curves, the degree of separation between negative and cutoff calibrators, precision, probability of carryover from positive to negative samples, and overall ease and speed of analysis were evaluated. EMIT II and OnLine were compared with RIA tests for the five drugs to determine each assay's ability to detect samples which confirm positive by GC/MS. The RIA and OnLine marijuana tests detected > 99% of confirmed positive samples while EMIT II detected about 90%. All three immunoassays performed equivalently for cocaine and opiates, each assay detecting at least 98% of positives. Barbiturates showed the greatest disparity with OnLine detecting 96%, EMIT II 85%, and RIA 79% of confirmed positive samples. Too few phencyclidine positive samples were detected for a method comparison study. The fully automated EMIT II and OnLine assays are preferable for a variety of reasons to our laboratory's current semi-automated RIA tests for large volume urine testing. The immunoassays offer comparable performance for some drugs but not for others.

In a case involving a fatal shooting, toxicology tests on blood and urine demonstrated the presence of cocaine metabolites and a large amount of an unidentified compound. This compound was subsequently identified by mass spectral, gas chromatographic, and thin layer chromatographic tests as laudanosine, a metabolite of the skeletal muscle relaxant atracurium which was administered during emergency surgery. Identification was confirmed by comparison with commercially available standards. Because of the difficulty associated with isolating and chromatographing highly water-soluble compounds, recognition of this artifact is a useful tool in identifying these cases.

A single-step extraction method and thin-layer identification techniques capable of testing a wide variety of drugs of abuse are presented. These techniques are well suited for large and/or small drug programs involved in urine testing because they provide substantial economic benefits and improve clinical functioning. The drugs are absorbed on a 6 X 6 cm piece of paper loaded with cation-exchange resin and then eluted from the paper at pH 10.1 using ammonium chloride-ammonia buffer. The simultaneous thin-layer detection of sedatives, hypnotics, narcotic analgesics, central nervous system stimulants and miscellaneous drugs is accomplished by spotting the solution of extracted residue on a 20 X 20 cm Gelman pre-coated silica gel glass microfiber sheet (ITLC Type SA). A two-stage solvent system is used in order to obtain a chromatogram with optimum separation of a wide range of drugs. This system can separate methadone and/or cocaine from propoxyphene, methaqualone, methylphenidate, pentazocine, pipradrol, Doxepin, chlorpromazine, phenazocine, naloxone, naltrexone, imipramine and trimeprazine; amphetamine from phenylpropanolamine and dimethyltryptamine; codeine from dextromethorphan; methamphetamine from dimethyltryptamine, etc. Different detection reagents are then applied in succession to different marked areas of the developed chromatogram. This elegant method of extraction and spraying has enabled us to detect morphine base at a sensitivity level of 0.15 mug/ml, amphetamine sulfate at 1.0 mug/ml, methamphetamine hydrochloride at 0.5 mug/ml, phenmetrazine hydrochloride at 0.5 mug/ml, codeine phosphate at 0.5 mug/ml, methadone hydrochloride at 1.0 mug/ml, secobarbital at 0.36 mug/ml and phenobarbital at 0.5 mug/ml in urine. The minimum volume of urine needed to achieve these sensitivities is 20 ml. The cost of analysis per urine specimen using these techniques for concomitant screening of these drugs is less than US$ 1.

Random testing of urine from opiate addicts in the methadone treatment programme at the Drug Dependency Service, Brisbane Street, Sydney, was carried out for 18 months. Six samples from each of approximately 100 clients (that is, 580 specimens) have been analysed. It was found that clients receiving high methadone dosages (80 mg and over) used illegal opiates significantly less frequently than those on lower dosages. Furthermore, a decline in the use of illegal opiates and an increase in the proportion of "clear" urine specimens (that is, clear of all drugs except methadone) were indicators of the effectiveness of the methadone programme. It was concluded that urine testing was a useful and objective means of evaluating methadone or any other drug addiction treatment programme, and of monitoring what other drugs were being taken, both consciously or inadvertently in combinations. The results of urine testing can also be of value to counsellors in the therapeutic situation.

A gas chromatographic-mass spectrometric assay for eight opium alkaloids in human urine following opium ingestion is described. The compounds were extracted from urine with methylene chloride-isopropanol (7:3, v/v) at pH 9.5, evaporated, derivatized with Tri-Sil Z and analyzed by methane chemical ionization mass fragmentography. The method in sensitive to ca. 0.01 microgram/ml for morphine and codeine and ca. 0.05 microgram/ml for the other compounds. Adsorption problems on the gas chromatography column prevented obtaining reproducible results for the measurement of noscapine. Extraction efficiencies over the pH range of 8-11 for the eight compounds are reported. Retention times of the opium alkaloids were determined using five different liquid phases (3%) on Gas-Chrom Q (100-120 mesh) and two column lengths (36 cm and 183 cm). The 36-cm column packed with OV-210 was selected for use in the assay. Ions were selected for monitoring for each component from their methane chemical ionization spectrum to provide the needed sensitivity and specificity for analysis of a multi-component mixture. The assay was used for the analysis of an "opium eater's" urine. Morphine, codeine, nomorphine, norcodeine and noscapine were detected; however, no evidence was obtained for thebaine, papaverine or oripavine. Unconjugated morphine (0.64 microgram/ml) was present at nearly twice the concentration of codeine (0.37 microgram/ml) and normorphine and norcodeine were present in equal amounts (ca. 0.15 microgram/ml).