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9 recordsLinked to original sources
PubMed2003

Liquid chromatographic-atmospheric pressure chemical ionization mass spectrometric analysis of opiates and metabolites in rat urine after inhalation of opium.

To examine the urinary excretion of opiates and their metabolites following inhalation exposure of rats to opium, analytical procedures for the simultaneous determination of the compounds in opium, the vapor derived by the volatilization of opium and the urine of rats exposed to the opium vapor were developed using liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS). Seven compounds were determined in the opium, namely morphine, codeine, thebaine, noscapine, papaverine, meconic acid and meconin. All seven were extracted with 2.5% acetic acid solution and subjected to LC-APCI-MS analysis. The separation was performed on an ODS column in acetonitrile-50 mM ammonium formate buffer (pH 3.0) using a linear gradient program and quantitative analysis was carried out in the selected ion monitoring mode ([M+H](+)). For the analysis of the volatilization of opium, the opium (1 g) was added to a glass pipe, which was then heated at 300 degrees C for 20 min. Negative pressure (air flow-rate; 300 ml/min) was used to draw the vapor through a series of glass wool and methanol traps. The total amount of each compound in the vapor was estimated by measurement of the compounds trapped in the glass wool and methanol. Wister rats (n=3) were exposed to the vapor derived from the volatilization system and the urinary amounts (0-72 h) of the six opiates and metabolites including morphine-3-grucronide (M3G) and morphine-6-grucronide (M6G) were measured after solid-phase extraction. The calibration curves for those compounds in the rat urine were linear over the concentration range 10-500 ng/ml. The recoveries for each analyte from the rat urine sample spiked with standard solution were generally greater than 80%, and the relative standard deviation for the analytical procedure was less than 8% with the exception of meconin. After inhalation exposure of rats to opium, M3G (5.45-14.38 micro g), morphine (2.27-4.65 micro g), meconin (0.54-1.85 micro g), codeine (0.54-1.85 micro g), noscapine (0.34-0.40 micro g) and papaverine (0.01-0.04 micro g) were detected in the urine over 72 h. However, only trace levels of thebaine were observed despite it being one of the major alkaloids found in the opium. On the other hand, a relatively large amount of meconin was detected in the vapor and the urine as compared with the opium. It is suggested that the presence of meconin in biological fluids could be indicative of opium ingestion by inhalation.

Administration, Inhalation↗
PubMed1979

Metabolic fate of noscapine. II. Isolation and identification of novel metabolites produced by C-C bond cleavage.

1. The metabolism of noscapine was studied in rabbits, rats and human. 2. Apart from the O-demethylated metabolites already reported, three metabolites were isolated and identified as meconine, cotarnine and hydrocotamine, respectively. 3. Mass fragmentography (chemical ionization) was used to determine these products simultaneously. 4. Meconine was the major metabolite in all three species, accounting for about 3, 8 and 2% of the dose in the first 24 h urines of rats, rabbits and humans, respectively, although one woman excreted to a very high extent (22%). In rats, cotarnine bases were excreted at almost same level as that of meconine, but at lesser extent in other two species. Hydrocotamine and unchanged noscapine were excreted to less than 1% dose.

Adult↗
PubMed2001

Diamorphine treatment for opiate dependence: putative markers of concomitant heroin misuse.

The supply of substitute opioid medication as a treatment for heroin dependence is now common practice. There is growing international interest in the prescription of injectable diamorphine for subgroups of patients who are unable to stop injecting opiate drugs; in the United Kingdom it is estimated that there are currently 300 patients prescribed diamorphine for this purpose. The detection of illicit heroin misuse (through urinary diamorphine metabolites) is confounded in subjects prescribed diamorphine. We investigated the potential to distinguish between the use of street heroin and pharmaceutical diamorphine through the detection in urine of various opiate alkaloids originating in the opium poppy, Papaver somniferum. Over a 7-week period, 532 clients of an urban substance misuse service provided a total of 1122 urine samples for clinical purposes. Using a novel mixed-mode solid-phase extraction and gas chromatography/mass spectrometry technique, we screened samples for morphine, 6-monoacetylmorphine, codeine, meconine, papaverine, noscapine, thebaine and their metabolites. All urine samples from diamorphine-treated patients were positive for morphine. Of samples from patients receiving other treatments, 30% (95%CI: 27-33%) were positive for morphine, indicating probable street heroin misuse. Of morphine-positive samples, 61% (95%CI: 55-67%), from the "other treatments" group were positive for at least one of codeine, meconine and putative noscapine or papaverine metabolites. This was reduced to 56% (95%CI: 50-62%) when excluding codeine. Only one sample (0.1%) was positive for any one of these putative markers in the absence of morphine, when excluding codeine. These findings show that the detection of urinary noscapine and papaverine metabolites is useful in distinguishing between use of pharmaceutical diamorphine and street heroin. This may be of benefit to promote safer and more effective prescribing of diamorphine in opiate dependency, and as an outcome measure in trials of diamorphine prescribing.

Journal Article↗
PubMed2006

Comparison of the various opiate alkaloid contaminants and their metabolites found in illicit heroin with 6-monoacetyl morphine as indicators of heroin ingestion.

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.

Administration, Oral↗
PubMed2005

Validation of techniques to detect illicit heroin use in patients prescribed pharmaceutical heroin for the management of opioid dependence.

BACKGROUND: The clinical implementation and evaluation of heroin substitution programmes have been confounded by the lack of objective and validated biomarkers for illicit heroin use in patients prescribed pharmaceutical heroin. This study examined the capacity to detect illicit heroin use by gas chromatography-mass spectrometry (GC-MS) analysis of urine samples for the presence of opium impurities common to illicit, but not pharmaceutical heroin. AIMS: To characterize the diagnostic properties of the metabolites of noscapine and papaverine in comparison to morphine as a gold-standard marker of illicit heroin use; and to examine the relationships between the self-reported time since most recent heroin use and the detection of these opioids in urine. DESIGN: A cross-sectional study of 52 opioid-dependent patients in treatment (not prescribed heroin), who self-reported illicit heroin use within the preceding 2 weeks. Self-report data regarding recent drug use and a urine sample were collected. GC-MS analyses of urines were conducted and reported by laboratory staff blinded to self-report data. FINDINGS: The metabolites of papaverine (hydroxypapaverine and dihydroxypapeverine) were found to have high sensitivity, specificity and negative predictive values as markers for illicit heroin use compared to the 'gold-standard' morphine. Other opioids, including 6-mono-acetylmorphine (6-MAM), codeine and noscapine metabolites (e.g. meconine) were less adequate in detecting heroin use. CONCLUSIONS: GC-MS detection of papaverine metabolites in urine appears to be suitable method of identifying illicit heroin use for clinical and research purposes.

Adult↗