[Correlation between insufficient methadone dosage and morphine positive urine on drop out of treatment in patients with access to methadone maintenance treatment].

Objective: To estimate the incidence of drop out of treatment in patients with access to methadone maintenance treatment and explore the correlation and interaction between insufficient methadone dosage and morphine positive urine on the drop out in Guangxi Zhuang Autonomous Region. Methods: Face to face interview was conducted in 1 031 patients at 3 methadone maintenance treatment clinics in Guangxi. Results: The study included 1 031 participants, 40.6% of them (419/1 031) had stopped treatment. The drop out rates in urine morphine positive group and methadone dosage<100 mg/d group were 57.6% (99/172) and 37.4% (347/929) respectively, higher than those in urine morphine negative group and methadone dosage ≥100 mg/d group (42.3%, 363/859, and 26.5%, 27/102). Orderly logistic regression analysis results showed that after adjusted factors, such as gender, age, marital status, ethnic group, patients who received a dosage less than 100 mg/day (OR=3.05, 95%CI: 1.84-5.06) and had morphine positive urine (OR=2.25, 95%CI: 1.59-3.19) were more likely to drop out of the treatment. Interaction analysis showed that dosage less than 100 mg/d and morphine positive urine during treatment had additive interaction (RERI=256.46, AP=0.87, S= 8.05) and multiplication interaction (OR=2.45, 95%CI: 1.71-3.49). Conclusion: Insufficient dosage and morphine positive urine were significantly correlated with drop out of treatment in patients with access to methadone maintenance treatment.

A combined liquid three-phase micro-extraction and differential pulse voltammetric method for preconcentration and detection of ultra-trace amounts of buprenorphine using a modified pencil electrode.

A combination of polytetrafluorethylene membrane-based liquid three-phase micro-extraction and voltammetry was used for the micro-separation and determination of buprenorphine. Type of the organic solvent used, pH levels of the donor and acceptor phases, salt concentration, extraction time, stirring rate, and electrochemical parameters as the essential factors affecting the liquid three-phase micro-extraction of buprenorphine were investigated. Differential pulse voltammetry exhibited two linear dynamic ranges of 1.0-109.0 pmol L(-1) and 0.109 nmol L(-1)-0.11 µmol L(-1) of buprenorphine and the detection limit was found to be as low as 0.6 pmol L(-1) of buprenorphine. Also, the effects of a number of common substances potentially interfering with selectivity were studied. The results indicate that the proposed method is highly selective and sensitive for buprenorphine detection in real samples such as human urine and plasma of both drug-addict and non-addict human subjects.

Desmopressin accelerates the rate of urinary morphine excretion and attenuates withdrawal symptoms in rats.

AIM: The aim of this study was to examine the effects of desmopressin on morphine withdrawal symptoms and vasopressin level in morphine-dependent subjects. METHODS: Wistar male rats were injected s.c. with morphine once per day for 5 consecutive days to induce morphine dependence. After morphine use ceased on day 5, an equal number of rats were assigned to one of four groups for either saline or desmopressin by either intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) injection. From days 5 to 10, urine was collected daily and tested for the presence of morphine, and withdrawal symptoms were monitored to assess the effects of desmopressin. RESULTS: Significant weight loss occurred among all morphine-addicted rats during the withdrawal period. With both methods (i.p. and i.c.v.), the period of urinary morphine excretion was shorter for the two groups that were given desmopressin (experimental groups) than the two groups that were not given desmopressin (control groups), and no significant difference in urinary morphine excretion was found between the two experimental groups. During the early stage of withdrawal, the severity of the withdrawal symptoms in the experimental groups was significantly lower than that in the control groups. CONCLUSION: Desmopressin decreases the extent of morphine withdrawal symptoms, indicating that this agent might be appropriate for treating morphine addiction. Desmopressin appears to reduce withdrawal symptoms not by exerting an anti-diuretic effect but rather by exerting an effect on the central nervous system.

Cation-selective exhaustive injection and sweeping micellar electrokinetic chromatography for analysis of morphine and its four metabolites in human urine.

A cation-selective exhaustive injection and sweeping micellar EKC (CSEI-Sweep-MEKC) was established to analyze morphine and its four metabolites, including codeine, normorphine (NM), morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G). After SPE, the urine samples were analyzed by this CE method. The phosphate buffer (75 mM, pH 2.5) containing 30% methanol was first filled into an uncoated fused-silica capillary (40 cm, 50 microm id), then a high-conductivity buffer (120 mM phosphate, 10.3 kPa for 99.9 s) followed. The pretreated urine sample was loaded by electrokinetic injection (10 kV, 600 s). The stacking and separation were performed by using phosphate buffer (25 mM, pH 2.5) containing 22% methanol and 100 mM SDS at -20 kV, and detected at 200 nm. During method validation, calibration plots were linear (r > or = 0.998) over a range of 30-3000 ng/mL for morphine, NM, and codeine, 100-2000 ng/mL for M6G, and 80-3200 ng/mL for M3G. The LODs (S/N = 5, sampling 600 s at 10 kV) were 10 ng/mL for morphine, NM, and codeine, 35 ng/mL for M6G, and 25 ng/mL for M3G. This stacking CE method could increase 2500-fold sensitivity of codeine, when comparing with CZE. Five addicts' urine specimens were analyzed. Their results were compared with those of LC-MS-MS, and showed good coincidence. This method could be feasible for monitoring morphine and its metabolites in forensic interest and pharmacokinetic investigations.

Urine drug test interpretation: what do physicians know?

OBJECTIVE: To determine the level of urine drug test (UDT) interpretive knowledge of physicians who use these instruments to monitor adherence in their patients on chronic opioid therapy. METHODS: A seven-question instrument consisting of six five-option, single-best-answer multiple choice questions and one yes/no question was completed by 114 physicians (77 who employ UDT and 37 who do not) attending one of three regional opioid education conferences. We calculated frequencies and performed chi2 analyses to examine bivariate associations between UDT utilization and interpretive knowledge. RESULTS: The instrument was completed by 80 percent of eligible respondents. None of the physicians who employ UDT answered all seven questions correctly, and only 30 percent answered more than half correctly. Physicians who employ UDT performed no better on any of the questions than physicians who do not employ UDT. CONCLUSIONS: Physicians who employ UDT to monitor patients receiving chronic opioid therapy are not proficient in test interpretation. This study highlights the need for improved physician education; it is imperative for physicians to work closely with certified laboratory professionals when ordering and interpreting these tests.

[Drug abuse among new draftees]. / Rusmiddelbrug blandt nyindkaldte vaernepligtige.

The aim of the study was to investigate the pattern of the use of drugs among young conscripts by a test screening of their urine. The participants in the investigation also filled in a questionnaire about use of drugs. The urine samples from 916 young recruits were examined for cannabinoids and 429 were also examined for amphetamines, cocaine, opiates and benzodiazepines. We found 68 (7.8%) positive tests for cannabis and a negligible number of positive tests for other drugs. The questionnaire showed a lower statement of use of drugs though 3.3% stated a daily or weekly use of cannabis. Fifty-eight percent of the soldiers admitted that they had tried cannabis. Six percent had used other drugs. The consumption of alcohol is low during weekdays. We concluded that the conscripts did not constitute a population of drug abusers. We recommend that urine test screening (regular or spot test) should be incorporated in the future medical examination in the Danish Army to pinpoint personnel with a moderate use of cannabis.

[Analytical exploration of drug addiction]. / Exploration analytique des toxicomanies.

The natural and synthetic substances most frequently leading to drug addiction are described. They include cannabis, opium and cocaine with their respective derivatives. The authors insist on the problems encountered by analytical chemists when they examine urine samples containing these substances, owing to their metabolic degradation and to interferences between lawful and unlawful drugs. The limitations imposed by these problems to an unambiguous interpretation of the results obtained are defined, but they do not throw any doubt on the value of these investigations.

A rapid, qualitative ELISA test for the specific detection of morphine in serum or urine.

We describe a competitive inhibition ELISA technique, with a visual end-point, to detect free morphine in blood or urine. It has a sensitivity of 2 X 10(-7) mol/l using 5 microliter samples. No significant cross-reactivity was observed with other opiate derivatives. The assay has applications as a specific screen for morphine in drug abusers, or to study the metabolism of the drug in the body (as the metabolite, morphine-3-glucuronide, does not cross-react significantly with morphine in the assay).

[Methodology and problems in the study of drugs of abuse in urine]. / Methodik und Problematik der Suchtgiftuntersuchung im Harn.

The analysis of drugs of abuse in urine is a valuable tool for the detection of illicit drug use and the treatment and rehabilitation of addicts. In order for the results to be conclusive, however, several precautions have to be taken during the collection, storage, mailing and analysis of the urinary specimen. Since immunological methods for the determination of drugs of abuse are not completely specific, all positive results on immunoassay should be confirmed, at least for forensic purposes, by a chromatographic technique. Although much more complicated and time-consuming, some chromatographic techniques such as gas chromatography-mass spectrometry offer the possibility of unambiguously identifying drugs of abuse. However, in some cases, even with this method it is not possible to decide whether the identified metabolite of a drug of abuse stems from food or illicit or elicit drug use. A single urinary analysis is, therefore, sometimes not sufficient to provide unambiguous proof of the use of illicit drugs. However, definite evidence of repeated drug abuse can be obtained if the person involved is carefully instructed as to which medicines or food must not be taken during the investigation period and yet the analysis of several urinary specimens taken at intervals of one or two days proves positive.

Radioimmunoassay of hair for determining opiate-abuse histories.

Heroin and morphine metabolites can be detected in hair with the use of commercially available radioimmunoassay reagents and with minor sample preparation. Hair samples obtained from morphine-treated mice and heroin users contained nanogram levels of the drug per milligram of hair (single human hair). The results of the hair analyses for all subjects admitting the use of heroin were positive, whereas the results of only 30% of thin-layer chromatographic urinanalyses of these same subjects were positive. In addition, differences in drug concentration for sections of hair near the scalp and near the distal end correlated with the length of time the drug had been used. These results exemplify the potential advantages of the use of hair analysis over urine and serum analyses in terms of accessibility, sample stability, and long-term retention of information.

Urine screening of arrestees as a source of drug abuse indicator data.

The National Institute on Drug Abuse (NIDA) recently sponsored a study which examined the utility of jail urine screening programs as a source of drug abuse indicator data. During the study, short-term urine screening programs were set up in the central jail facilities of four urban counties. To determine whether jail urine screening programs have the capacity to detect patterns of drug use not readily detectable through existing indicators, the urinalysis findings for each county were compared with data generated by the DAWN and CODAP systems. The results of the study suggest that jail urine screening programs can be useful as a supplement to existing sources of information on drug use patterns in local communities.

Isolation and identification of morphine 3- and 6-glucuronides, morphine 3,6-diglucuronide, morphine 3-ethereal sulfate, normorphine, and normorphine 6-glucuronide as morphine metabolites in humans.

Morphine metabolites were isolated with column chromatography on a resin and neutral aluminum oxide and TLC from the urine of morphine-dependent subjects maintained on morphine sulfate at a dose of 240 mg/day. These metabolites were characterized as morphine 3-glucuronide, morphine 6-glucuronide, morphine 3,6-diglucuronide, morphine 3-ethereal sulfate, normorphine, normorphine 6-glucuronide, and, possibly, normorphine 3-glucuronide by free phenol and glucuronide tests, enzymatic hydrolysis, GLC, TLC, UV spectroscopy, and GLC--mass spectrometry.

Radioimmunological detection of morphine in stains of blood and urine.

Morphine in blood and urine spots was detected by the radioimmunoassay (125-J-Abuscreen R, Hoffmann La Roche) in nanogram quantities. Blood and urine drops containing morphine (5 or 20ng) were dropped on wood, fired clay or cotton and stored for perios of 1 to 21 days in a dry or humid environment. Detection in blood stains on cotton was achieved in all cases. Results were more variable in blood spots on clay or wood, but in most cases detection was possible. In urine, morphine was detectable only on cotton. The differences are explained by different degrees of adsorption of blood and urine on the materials and the difficulties of elution thereof.

[Detection and quantitative estimation of morphine in the urine of drug addicts by combined 2-dimensional thin-layer chromatography and spectrofluorometry]. / Détection et estimation quantitative de la morphine dans l'urine des toxicomanes par couplage chromatographie bidimensionnelle sur couche mince--spectrofluorimétrie

Following extraction from urine and thin-layer bidimensional chromatography, the suspected spot of morphine is located by UV examination at 350 nm and eluted with methanol by means of "Eluchrom" apparatus. The dried residue is then subjected to spectrofluorimetric analysis, in definite conditions. This procedure can be used to confirm the identification of the alkaloid and to achieve its estimation. The sensitivity and the recoveries of various quantities of morphine added to urine were determined.

Comparison of results for morphine urinalyses by radioimmunoassay and thin-layer chromatography in a narcotic clinic setting.

Radioimmunoassay (RIA) and thin-layer chromatography (TLC) were compared for morphine detection in an actual narcotic clinic setting. A choice of urines from all those screened by TLC allowed a critical comparison as to actual use or non-use of narcotic drugs, rather than a sampling at random in which the question of possible false positives or negatives cannot be conclusively answered. Although RIA is more sensitive than TLC, its advantage is apparent only in those cases where urine specimens are difficult to obtain frequently regularly or where the use of morphine is suspected by the positive identification of quinine in urine that was morphine-negative by TLC. In a selected group of negative and positive specimens chosen without conscious bias, the two methods gave consistently similar results, indicating that the modified TLC method provided a few or no false positives or negatives if the negatives were from those cases that were not positive anytime up to 3-4 days before urine collection. We conclude that RIA can be of significant value as a supplement to a TLC screening program, without sacrificing the many advantages that TLC has to offer.

Urinary excretion of morphine and its metabolites in morphine-dependent subjects.

Morphine, morphine glucuronide, morphine ethereal sulfate, normorphine and total normorphine in three consecutive 24-hour urines of four morphine-dependent subjects receiving morphine sulfate 60 mg s.c. q.i.d. have been determined with thin-layer chromatography and gas-liquid chromatography. With thin-layer chromatography the mean daily excretion of free morphine was 10% of the administered dose; morphine glucuronide, 65%; total (free and acid hydrolyzable conjugate) morphine 85%; and total normorphine, 3.5%. With gas-liquid chromatography, the percentage excretion for free morphine was 10%; total morphine, 74%; free normorphine, 1%; and total normorphine, 4%. The excretion of total drug was linearly related to the volume of the daily urine output.