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At least 1,477 records · Page 82Linked to original sources
PubMed1993

Simultaneous determination of drugs of abuse (opiates, cocaine and amphetamine) in human hair by GC/MS and its application to a methadone treatment program.

A new method was developed for the simultaneous detection and quantitation of 6-acetyl-morphine (MAM), amphetamine, benzoylecgonine (BZE), cocaine, codeine, dihydrocodeine, EDDP (methadone metabolite), methadone and morphine in hair. The hair samples were washed, cut into 2-cm segments, pulverized, incubated with phosphate buffer and beta-glucuronidase/aryl-sulfatase. After solid phase extraction and derivatization with pentafluoropropionic anhydride/pentafluoropropanol, the drugs were identified and measured by gas chromatography/mass spectrometry using their deuterated analogues as internal standards. The method is reproducible with detection limits under 0.1 ng/mg hair for almost all substances tested. Fifteen hair samples from five subjects of a methadone treatment program were collected in a 6-month period. The hair samples were segmented and examined for methadone, its main metabolite EDDP, and drugs of abuse. Of the 96 segments analysed, 95% were positive for methadone (mean value, 10.9 ng/mg), 76% for the metabolite EDDP (mean value, 1.2 ng/mg), 69% for opiates (mean values, MAM, 7.3 ng/mg; morphine, 2.9 ng/mg; codeine, 1.0 ng/mg) and 43% for cocaine (mean values, cocaine, 2.6 ng/mg; BZE, 1.1 ng/mg). A correlation of 0.63 was found between administered methadone dosages and concentrations measured by hair analysis. Further investigation is needed to clarify interindividual differences.

Adult↗
PubMed2004

The GC-MS detection and characterization of reticuline as a marker of opium use.

Reticuline (a precursor of opium alkaloids) was detected and characterised as its trimethylsilyl ethers, acetyl esters and methyl ethers by GC-EIMS and GC-CIMS in opium and the urine of opium users after hydrolysis by acid or beta-glucuronidase as coextractive of morphine. Because this compound cannot be detected in heroin and poppy seeds, it is suggested as a differentiating marker between opium and heroin use, opium and poppy seeds use, or opium and "pharmaceutical" codeine use in cases when opiate use has been confirmed by detection of morphine and codeine in the urine. As well as being a constituent of opium, reticuline in the urine of opium users may also result from the metabolic demethylation of the three other benzyltetrahydroisoquinoline opium alkaloids: codamine, laudanosine and laudanine.

Alkaloids↗
PubMed2004

The GC-MS detection and characterization of reticuline as a marker of opium use.

Reticuline (a precursor of opium alkaloids) was detected and characterised as its trimethylsilyl ethers, acetyl esters and methyl ethers by GC-EIMS and GC-CIMS in opium and the urine of opium users after hydrolysis by acid or beta-glucuronidase as coextractive of morphine. Because this compound cannot be detected in heroin and poppy seeds, it is suggested as a differentiating marker between opium and heroin use, opium and poppy seeds use, or opium and "pharmaceutical" codeine use in cases when opiate use has been confirmed by detection of morphine and codeine in the urine. As well as being a constituent of opium, reticuline in the urine of opium users may also result from the metabolic demethylation of the three other benzyltetrahydroisoquinoline opium alkaloids: codamine, laudanosine and laudanine.

Alkaloids↗
PubMed2006

Application of pericardial fluid to the analysis of morphine (heroin) and cocaine in forensic toxicology.

In this study opiates (morphine and codeine) and cocaine and its related metabolites (benzoylecgonine and cocaethylene) were analyzed in pericardial fluid by GC/MS. This is the first study reporting levels of drugs of abuse in this body fluid. The analytical method used has been previously validated and then applied to 54 drug-related deaths in the Barcelona area (Spain). Median levels were as follows: morphine 589ng/ml, range 19-8857 (n=49); codeine 26ng/ml, range 15-343 (n=35); cocaine 78ng/ml, range 10-220 (n=14), benzoylecgonine 742ng/ml, range 20-3386 (n=15), and cocaethylene 36ng/ml, range 9-100 (n=13). In addition, a comparative study of the concentration of opiates and cocaine in pericardial fluid by both semi-quantitative EMIT d.a.u. and GC/MS (used as reference) was performed. Fairly good correlations for opiates (r=0.905) and cocaine (r=0.859) were found; however, the consistently low results of EMIT in the analysis of cocaine comparing to GC/MS could be caused by matrix effect. In spite of that, it raises the possibility of using the immunoassay as a preliminary technique in forensic toxicology.

Cocaine↗
PubMed2005

Ionic liquid-based aqueous two-phase system, a sample pretreatment procedure prior to high-performance liquid chromatography of opium alkaloids.

An ionic liquid, 1-butyl-3-methylimidazolium chloride ([C4 mim]Cl)/salt aqueous two-phase systems (ATPS) was presented as a simple, rapid and effective sample pretreatment technique coupled with high-performance liquid chromatography (HPLC) for analysis of the major opium alkaloids in Pericarpium papaveris. To find optimal conditions, the partition behaviors of codeine and papaverine in ionic liquid/salt aqueous two-phase systems were investigated. Various factors were considered systematically, and the results indicated that both the pH value and the salting-out ability of salt had great influence on phase separation. The recoveries of codeine and papaverine were 90.0-100.2% and 99.3-102.0%, respectively, from aqueous samples of P. papaveris by the proposed method.

Chemical Fractionation↗
PubMed2005

Functional and morphological organization of the nucleus tractus solitarius in the fictive cough reflex of guinea pigs.

Projection of the superior laryngeal nerve (SLN) afferent fibers into the nucleus tractus solitarius (NTS) was investigated using a fluorescent tracer in guinea pigs. High density of fluorescence was detected in the ipsilateral NTS extending from 0.5 mm caudal to 1.2 mm rostral to the obex. At coronal slices, the fluorescent granules, lines and patches were located in the interstitial, medial and dorsal regions of NTS. Fluorescence was also found in the dorsal region of contralateral commissural NTS. Microstimulation of the rostral NTS, which corresponded to the region showing the strong fluorescence, induced an increase in the inspiratory discharge of phrenic nerve that was immediately followed by a large burst discharge of the iliohypogastric nerve in decerebrate, paralyzed and artificially ventilated guinea pigs. This serial response of the two nerves was identical to that induced by electrical stimulation of the SLN. Intravenous injection of codeine suppressed both NTS and SLN-induced responses. The SLN-induced response was inhibited by microinjection of codeine into the ipsilateral NTS and abolished by lesion of the ipsilateral NTS. These results suggest that the NTS has an integrative function in production of cough reflex and is possible sites of action of central antitussive agents.

Animals↗
PubMed1999

Antitussive effect of K+ channel openers.

The effect of the K(ATP) channel openers, pinacidil and cromakalim, on coughing was studied in guinea pigs exposed to a nebulized aqueous solution of citric acid (0.50 M). Both pinacidil and cromakalim, subcutaneously administered 45 min before the test, inhibited coughing. The D50 (95% CI) were 0.95 +/- 0.90 mg/kg for cromakalim and 3.25 +/- 0.92 mg/kg for pinacidil. Under our experimental conditions, the D50 (95% CI) of codeine was 1.74 +/- 0.75 mg/kg. The combination of cromakalim and pinacidil with codeine produced an additive effect. An additive effect was also produced by the combination of pinacidil with the selective tachykinin NK2 receptor antagonist MEN 10,627 = [cyclo(Met-Asp-Trp-Phe-Dap-Leu)cyclo(2beta-5beta)]. The antitussive effect of pinacidil and cromakalim was not a consequence of a bronchodilating effect, which was absent at these dose levels under our experimental conditions. These results indicate that K(ATP) channel openers have an opioid-like antitussive effect and may suggest a novel approach to the symptomatic treatment of coughing.

Animals↗
PubMed1976

Liquid chromatography of dansyl derivatives of some alkaloids and the application to the analysis of pharmaceuticals.

Derivatization of the alkaloids cephaeline, codeine, emetine, ephedrine, morphine, narcotine and others with dansyl chloride has been studied with the aim of developing a sensitive and specific liquid chromatographic method for these substances in complex pharmaceutical dosage forms. While codeine and narcotine do not react, the other compounds form completely substituted derivatives which possess maxima in their fluorescence emission spectra between 470 and 500 nm. The structure of the derivatives has been confirmed by nuclear magnetic resonance spectroscopy. The dansylated compounds have been separated by thin-layer chromatography and high-pressure liquid chromatography. The improved selectivity and sensitivity have permitted an analysis of these substances present in low concentrations in 10- 100-fold excesses of other drugs. Direct derivatization of syrups and aqueous slurries of capsules having a complex excipient and drug composition is feasible and time saving and serves as a pre-clean-up step. Detection limits are in the 1-10-ng range or better, depending on the efficiency of the detection device. The reproducibility of the method is limited by the derivatization step, but a relative standard deviation of less than 2% can be obtained. The analysis time for these pharmaceuticals may be reduced by at least one fifth of that required by conventional techniques.

Alkaloids↗
PubMed1992

Morphine metabolism in acutely ill preterm newborn infants.

To examine the manner in which morphine is metabolized in acutely ill premature infants, we measured the levels of morphine, morphine-3- and -6-glucuronides, and codeine in timed urine specimens and paired plasma specimens at 4 hours and 24 hours after a single dose of morphine in 16 preterm infants (less than 32 weeks of gestational age). A large amount of unmetabolized morphine was found in the urine in 13 (81.2%) of the 16 infants at 4 hours; in 12 of them, morphine was excreted even at 24 hours. Urinary morphine levels varied greatly; the coefficient of variation was 130% at 4 hours and 118% at 24 hours. Codeine was not found in any of the infants. In 10 (62.5%) of the 16 infants, at least one metabolite was found in either plasma or urine. Plasma and urinary levels of morphine conjugates also varied greatly among these 10 infants (coefficient of variation: 109% to 317%). All six infants (37.5%) who had no metabolites excreted large amounts of unmetabolized morphine in the urine for up to 24 hours. Birth weight, gestational age, postnatal age, systemic blood pressure, and other clinical or physiologic variables did not differ significantly between the 10 infants who had morphine conjugates and the six who did not. We conclude that (1) nearly two thirds of acutely ill preterm infants born at less than 32 weeks of gestational age conjugate morphine; (2) irrespective of their ability to produce morphine conjugates, preterm infants excrete large amounts of morphine unmetabolized, as late as 24 hours after a single dose; (3) morphine handling patterns are highly variable among premature infants, and no obvious factors account for the variability; and (4) such variability in morphine handling in general, and the production of the highly potent morphine-6-glucuronide in particular, could explain the variance in morphine pharmacokinetic measures and in the clinical responses to morphine during the newborn period.

Chromatography, High Pressure Liquid↗
PubMed1990

Determinants of in vivo histamine release in cutaneous allergic reactions in humans.

To determine host factors influencing the magnitude of mediator release during ongoing cutaneous allergic reactions in humans, we compared, in 22 subjects, the first-hour, second- to fifth-hour, and total (0 to 5 hours) skin chamber histamine release to (1) the in vitro reactivity and sensitivity of basophils to antigen for histamine release and (2) skin test sensitivity and reactivity to antigen, histamine, and codeine. There was no significant correlation between the first-hour and second- to fifth-hour histamine release. With a combination of basophil, antigen, histamine, and codeine skin sensitivity and reactivity, 64% to 75% of the magnitude of the first-hour, second- to fifth-hour, and total (0 to 5 hours) skin chamber histamine release could be accounted for. We conclude that antigen-induced in vivo allergic responses are a complex phenomenon dependent, in part, on antigen sensitivity, basophil and mast cell reactivity, and end organ responsiveness to mediators.

Adolescent↗
PubMed1996

Long-term oral corticosteroid therapy does not alter the results of immediate-type allergy skin prick tests.

BACKGROUND: Medications can modulate the results of skin prick tests (SPTs). Short-term corticosteroid therapy does not alter IgE-mediated skin tests, but the impact of long-term oral corticosteroid therapy on SPT results is unclear. A prospective study was carried out in patients with steroid-dependent asthma who received oral corticosteroids for a long period to determine whether this treatment reduced skin test reactivity. METHODS: Thirty-three patients with steroid-dependent asthma (median age, 59 years) were compared with 66 patients with asthma who served as a control group, matched for age, sex, and atopic status. SPTs with codeine phosphate and a screening battery of standardized allergen extracts were performed before commencement and after at least 1 year of daily oral prednisone treatment (median duration, 2 years; median daily dose, 20 mg). RESULTS: Fifteen patients with corticosteroid-dependent asthma were allergic before treatment, and their sensitization was not changed by long-term treatment with oral corticosteroids. The median wheal diameters induced by codeine phosphate were similar in both groups. The median wheal diameters induced by allergens, and more specifically, by Dermatophagoides pteronyssinus and D. farinae were similar in both groups and did not change in the steroid group after treatment. CONCLUSIONS: Systemic corticosteroid therapy (prednisone, 10 to 60 mg/day) for 2 or more years does not seem to alter SPT reactivity.

Adult↗
PubMed2002

Quantitative determination of amphetamines, cocaine, and opiates in human hair by gas chromatography/mass spectrometry.

Hair of young subjects (N = 36) suspected for drug abuse was analysed for morphine, codeine, heroin, 6-acetylmorphine, cocaine, methadone, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA). The analysis of morphine, codeine, heroin, 6-acetylmorphine, cocaine, and methadone in hair included incubation in methanol, solid-phase extraction, derivatisation by the mixture of propionic acid anhydride and pyridine, and gas chromatography/mass spectrometry (GC/MS). For amphetamine, methamphetamine, MDA, MDMA, and MDEA analysis, hair samples were incubated in 1M sodium hydroxide, extracted with ethyl acetate, derivatised with heptafluorobutyric acid anhydride (HFBA), and assayed by GC/MS. The methods were reproducible (R.S.D. = 5.0-16.1%), accurate (85.1-100.6%), and sensitive (LoD = 0.05-0.30ng/mg). The applied methods confirmed consumption of heroin in 18 subjects based on positive 6-acetylmorphine. Among these 18 heroin consumers, methadone was found in four, MDMA in two, and cocaine in two subjects. Cocaine only was present in two, methadone only in two, methamphetamine only in two, and MDMA only in seven of the 36 subjects. In two out of nine coloured and bleached hair samples, no drug was found. Despite the small number of subjects, this study has been able to indicate the trend in drug abuse among young people in Croatia.

Adolescent↗
PubMed1998

The detection of acetylcodeine and 6-acetylmorphine in opiate positive urines.

Acetylcodeine (AC), an impurity of illicit heroin synthesis, was investigated as a urinary biomarker for detection of illicit heroin use. One hundred criminal justice urine specimens that had been confirmed positive by GC/MS for morphine at concentrations > 5000 ng/ml were analyzed for AC, 6-acetylmorphine (6AM), codeine, norcodeine and morphine. The GC/MS analysis was performed by solid phase extraction and derivatization with propionic anhydride. Total codeine and morphine concentrations were determined by acid hydrolysis and liquid/liquid extraction. AC was detected in 37 samples at concentrations ranging from 2 to 290 ng/ml (median, 11 ng/ml). 6AM was also present in these samples at concentrations ranging from 49 to 12 600 ng/ml (median, 740 ng/ml). Of the 63 specimens negative for AC, 36 were positive for 6AM at concentrations ranging from 12 to 4600 ng/ml (median, 124 ng/ml). When detected, the AC concentrations were an average of 2.2% (0.25 to 10.2%) of the 6AM concentrations. There was a positive relationship between AC concentrations and 6AM concentrations (r = 0.878). Due to its very low concentration in urine, AC was found to be a much less reliable biomarker for illicit heroin use than 6AM in workplace or criminal justice urine screening programs. However, AC detection could play an important role in determining if addicts in heroin maintenance programs are supplementing their supervised diacetylmorphine doses with illicit heroin.

Biomarkers↗
PubMed1987

Ibuprofen given pre- and post-operatively for the relief of pain.

155 patients undergoing surgical removal of lower third molars took part in a parallel group, randomised double-blind study to assess the analgesic effect of single pre-operative doses of ibuprofen (400 mg), codeine phosphate (30 mg), a combination of ibuprofen/codeine (400 mg/30 mg), placebo and post-operative single doses of the same combination or diflunisal (250 mg). Patients receiving the combination or ibuprofen pre-operatively took significantly longer between surgery completion and needing the post-operative study treatment than patients receiving codeine phosphate or placebo. At 1 1/2-2 h after post-operative administration, patients receiving the combination post-operatively reported significantly greater decreases in pain severity than those receiving diflunisal. Patients taking the combination post-operatively experienced significantly better pain relief than patients taking diflunisal at 1 and 2 h, but the reverse was true at 5 h. Side-effects reported were mild with no significant differences between the different treatment groups.

Adolescent↗
PubMed2005

One-step homogeneous immunoassay for small analytes.

We have developed a one-step, homogeneous noncompetitive immunoassay for small analytes using recombinant antibodies and morphine as the model analyte. A highly specific antibody against the immune complex (IC) formed between an anti-morphine antibody and morphine was selected from a naive scFv phage display library. The in vitro phage library selection procedure avoids the difficulties associated with the production of anti-IC antibodies by animal immunization. The anti-morphine and the anti-IC antibodies were labeled with a pair of fluorescence resonance energy transfer (FRET) fluorophores. In the FRET assay the labeled antibodies were incubated with saliva samples spiked with morphine, codeine, or heroin. Within 2 min, 5 ng/mL morphine, which is clearly under the recommended cutoff level, was detected without cross-reactivity to codeine or heroin. This assay principle is also widely applicable to other small analytes.

Amino Acid Sequence↗
PubMed2005

14-Hydroxylation of opiates: catalytic direct autoxidation of codeinone to 14-hydroxycodeinone.

Codeinone (3) was efficiently and directly converted to 14-hydroxycodeinone (1) by catalytic air oxidation in aqueous solution. A number of simple manganese and copper salts were identified to be effective catalysts, including MnSO4, KMnO4, and CuSO4. An appropriate reducing agent, such as sodium thiosulfate, is required in the reaction mixture presumably for the reduction of a detrimental peroxide intermediate. This discovery allows the more abundant codeine to be employed as the starting material for the synthesis of 14-hydroxylated opiate drugs without recourse to a thebaine-like intermediate. These discoveries were inspired from our study of microbial transformation of codeine to 14-hydroxycodeine by Mycobacterium neoaurum, where we found the actual 14-hydroxylation step is a chemical reaction rather than an enzymatic reaction, as previously believed.

Catalysis↗
PubMed2005

Comparative qualitative and quantitative determination of alkaloids in narcotic and condiment Papaver somniferum cultivars.

In the present study morphinan, tetrahydrobenzylisoquinoline, benzo[c]phenanthridine, and phthalideisoquinoline alkaloids were determined qualitatively and quantitatively by HPLC and LC-MS analysis in tissues of the Tasmanian Papaver somniferum L. elite cultivar C048-6-14-64. The data were compared with the results from the low-morphine cultivar "Marianne". In the elite cultivar, 91.2% of the latex alkaloids consist of the three pharmaceutically most valuable alkaloids: morphine, codeine, and thebaine. In the root system, the major alkaloids are sanguinarine/10-hydroxysanguinarine and dihydrosanguinarine/10-hydroxydihydrosanguinarine. In the stems and leaves of C048-6-14-64, the same alkaloids were measured as in the latex. In the stems, a gradient in relative total alkaloid content from the top downward toward the roots was observed. The concentration of morphine was decreasing toward the roots, whereas an increasing gradient from the upper to the lower stem parts was detected for codeine. The relative total alkaloid concentration in leaves remained constant; no gradient was observed. The cultivar "Marianne" displayed a shifted pattern of alkaloid accumulation and reduced levels of total alkaloid. In the condiment cultivar, 80.5% of the alkaloids of the latex consisted of the two phthalideisoquinoline alkaloids narcotoline and noscapine. Only 18.8% of the relative total alkaloid content were morphinan alkaloids. In contrast to the narcotic cultivar, in which the benzo[c]phenanthridines in roots dominated over the morphinan and tetrahydrobenzylisoquinoline alkaloids, the concentration of benzo[c]phenanthridines in "Marianne" was similar to that of morphinan and tetrahydrobenzylisoquinoline alkaloids. These data suggest a differential alkaloid regulation in each cultivar of P. somniferum.

Alkaloids↗
PubMed1996

Opioid addiction and suicidality.

The prevalence of suicide attempts among opioid addicts is reported to lie between 8% and 17%, with some studies reporting an even higher rate among special groups of addicts. Yet there is insufficient knowledge about which addicts have a higher risk of suicide and which other factors seem to be involved in the constellation leading to the suicide attempt; the study of different subgroups of addicts is thus necessary. This paper reports a study on suicide attempts among a sample population in a detoxification unit and another group undergoing codeine maintenance treatment. There was a high rate of suicide attempts among both groups (23% of those in the detoxification unit and 28% of those maintained on codeine), but treating physicians tended to underestimate suicidality. The results lead to the conclusion that among a subgroup of addicts suicidality plays a larger role; a greater emphasis should thus be placed on the underlying psychopathology and the treatment needed.

Adult↗