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Olof Beck - One of the best experts on this subject based on the ideXlab platform.
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Direct and efficient liquid chromatographic-tandem mass spectrometric method for opiates in urine drug testing – importance of 6-acetylmorphine and reduction of analytes
Drug Testing and Analysis, 2013Co-Authors: Maria Andersson, Nikolai Stephanson, Tommy Terzuoli, Jonatan D. Lindh, Inger Öhman, Olof BeckAbstract:Opiates comprise a class of abused drugs that is of primary interest in clinical and forensic urine drug testing. Determination of heroin, codeine, or a multi-drug ingestion is complicated since both heroin and codeine can lead to urinary excretion of free and conjugated morphine. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) offers advantage over gas chromatography-mass spectrometry by simplifying sample preparation but increases the number of analytes. A method based on direct injection of five-fold diluted urine for confirmation of morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine, Codeine-6-Glucuronide and 6-acetylmorphine was validated using LC-MS/MS in positive electrospray mode monitoring two transitions using selected reaction monitoring. The method was applied for the analysis of 3155 unknown urine samples which were positive for opiates in immunochemical screening. A linear response was observed for all compounds in the calibration curves covering more than three orders of magnitude. Cut off was set to 2 ng/ml for 6-acetylmorphine and 150 ng/ml for the other analytes. 6-Acetylmorphine was found to be effective (sensitivity 82%) in detecting samples as heroin intake. Morphine-3-glucuronide and Codeine-6-Glucuronide was the predominant components of total morphine and codeine, 84% and 93%, respectively. The authors have validated a robust LC-MS/MS method for rapid qualitative and quantitative analysis of opiates in urine. 6-Acetylmorphine has been demonstrated as a sensitive and important parameter for a heroin intake. A possible interpretation strategy to conclude the source of detected analytes was proposed. The method might be further developed by reducing the number of analytes to morphine-3-glucuronide, Codeine-6-Glucuronide and 6-acetylmorphine without compromising test performance. Copyright © 2013 John Wiley & Sons, Ltd.
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Direct and efficient liquid chromatographic-tandem mass spectrometric method for opiates in urine drug testing – importance of 6-acetylmorphine and reduction of analytes
Drug testing and analysis, 2013Co-Authors: Maria Andersson, Nikolai Stephanson, Tommy Terzuoli, Jonatan D. Lindh, Inger Öhman, Olof BeckAbstract:Opiates comprise a class of abused drugs that is of primary interest in clinical and forensic urine drug testing. Determination of heroin, codeine, or a multi-drug ingestion is complicated since both heroin and codeine can lead to urinary excretion of free and conjugated morphine. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) offers advantage over gas chromatography-mass spectrometry by simplifying sample preparation but increases the number of analytes. A method based on direct injection of five-fold diluted urine for confirmation of morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine, Codeine-6-Glucuronide and 6-acetylmorphine was validated using LC-MS/MS in positive electrospray mode monitoring two transitions using selected reaction monitoring. The method was applied for the analysis of 3155 unknown urine samples which were positive for opiates in immunochemical screening. A linear response was observed for all compounds in the calibration curves covering more than three orders of magnitude. Cut off was set to 2 ng/ml for 6-acetylmorphine and 150 ng/ml for the other analytes. 6-Acetylmorphine was found to be effective (sensitivity 82%) in detecting samples as heroin intake. Morphine-3-glucuronide and Codeine-6-Glucuronide was the predominant components of total morphine and codeine, 84% and 93%, respectively. The authors have validated a robust LC-MS/MS method for rapid qualitative and quantitative analysis of opiates in urine. 6-Acetylmorphine has been demonstrated as a sensitive and important parameter for a heroin intake. A possible interpretation strategy to conclude the source of detected analytes was proposed. The method might be further developed by reducing the number of analytes to morphine-3-glucuronide, Codeine-6-Glucuronide and 6-acetylmorphine without compromising test performance.
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Evaluation of a direct high-capacity target screening approach for urine drug testing using liquid chromatography–time-of-flight mass spectrometry
Journal of Chromatography B, 2012Co-Authors: Aljona Saleh, Nikolai Stephanson, Ingrid Granelli, Tomas Villen, Olof BeckAbstract:Abstract In this study a rapid liquid chromatography–time-of-flight mass spectrometry method was developed, validated and applied in order to evaluate the potential of this technique for routine urine drug testing. Approximately 800 authentic patient samples were analyzed for amphetamines (amphetamine and methamphetamine), opiates (morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine and Codeine-6-Glucuronide) and buprenorphines (buprenorphine and buprenorphine-glucuronide) using immunochemical screening assays and mass spectrometry confirmation methods for comparison. The chromatographic application utilized a rapid gradient with high flow and a reversed phase column with 1.8 μm particles. Total analysis time was 4 min. The mass spectrometer operated with an electrospray interface in positive mode with a resolution power of >10,000 at m/z 956. The applied reporting limits were 100 ng/mL for amphetamines and opiates, and 5 ng/mL for buprenorphines, with lower limits of quantification were 2.8–41 ng/mL. Calibration curves showed a linear response with coefficients of correlation of 0.97–0.99. The intra- and interday imprecision in quantification at the reporting limits were
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electrospray lc ms method with solid phase extraction for accurate determination of morphine codeine and ethylmorphine glucuronides and 6 acetylmorphine in urine
Journal of Analytical Toxicology, 2007Co-Authors: J O Svensson, E. Gustavsson, Maria Andersson, Olof BeckAbstract:I human urine based on solid-phase extraction (SPE) and electrospray ionization liquid chromatography-mass spectrometry (LC-MS) was validated for use as a confirmation procedure in combination with immunochemical screening for opiates. Three deuterium-labelled analogues were used as internal standards: morphine-3- glucuronide-d3, codeine-d3, and 6-acetylmorphine-d3. Fifty- microliter aliquots of urine were prepared by SPE using 30-mg Oasis HLB cartridges. The chromatographic system consisted of a 2.0 x 100-ram C18 column and the gradient elution buffers used acetonitrile and 25 mmol/L formic acid. The protonated molecular ions were monitored in the selected ion monitoring mode together with one qualifier ion for each analyte. The variability was less than 10% at the reporting limit 30 ng/mL for 6-acetylmorphine and 300 ng/mL for the other analytes. The method was validated by comparison with a reference gas chromatographic (GC)-MS method using authentic urine samples. The two methods agreed completely regarding identified analytes, and for the quantitative results there were slightly lower levels when measuring glucuronides directly as compared to total determination after hydrolysis by GC-MS. This result was to be expected because the free compounds are not measured with the LC-MS method. This study concludes that the presented LC-MS
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Validation of direct injection electrospray LC-MS/MS for confirmation of opiates in urine drug testing
Journal of mass spectrometry : JMS, 2007Co-Authors: E. Gustavsson, Nikolai Stephanson, Maria Andersson, Olof BeckAbstract:A method based on the direct injection of diluted urine for the identification and quantification of morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine, Codeine-6-Glucuronide, ethylmorphine, ethylmorphine-6-glucuronide and 6-acetylmorphine (6AM) in human urine by electrospray ionisation liquid chromatography-tandem mass spectrometry was validated for use as a confirmation procedure in urine drug testing. Four deuterium labelled analogues were used as internal standards: morphine-3-glucuronide-D3, morphine-D3, codeine-D3 and 6AM-D3. Twenty microlitre aliquots of urine were mixed with 80 μl of the internal standard solution in autosampler vials and 10 μl was injected. The chromatographic system consisted of a 2.0 × 100 mm C18 column and the gradient elution buffers used acetonitrile and 25 mmol/l formic acid. Two product ions produced from the protonated molecular ions were monitored in the selected reaction monitoring mode. The intra- and inter-assay variability (coefficient of variation) was below 10% at higher levels for all analytes, but at the reporting limits the variation was above 20% for 6AM, morphine-3-glucuronide and Codeine-6-Glucuronide. Ion suppression occurred early after injection but did not affect the identification and quantification of the analytes in authentic samples. The method was further validated by comparison with a reference gas chromatographic-mass spectrometric method using authentic urine samples. The two methods agreed almost completely (99%) regarding the identified analytes, but for the quantitative results there were slightly lower levels when measuring glucuronides directly as compared to total determination after hydrolysis by gas chromatography-mass spectrometry. We conclude that the presented liquid chromatographic-tandem mass spectrometric method is robust and reliable, and suitable for use as a confirmation method in urine drug testing for opiates Copyright © 2007 John Wiley & Sons, Ltd.
Maria Andersson - One of the best experts on this subject based on the ideXlab platform.
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Direct and efficient liquid chromatographic-tandem mass spectrometric method for opiates in urine drug testing – importance of 6-acetylmorphine and reduction of analytes
Drug Testing and Analysis, 2013Co-Authors: Maria Andersson, Nikolai Stephanson, Tommy Terzuoli, Jonatan D. Lindh, Inger Öhman, Olof BeckAbstract:Opiates comprise a class of abused drugs that is of primary interest in clinical and forensic urine drug testing. Determination of heroin, codeine, or a multi-drug ingestion is complicated since both heroin and codeine can lead to urinary excretion of free and conjugated morphine. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) offers advantage over gas chromatography-mass spectrometry by simplifying sample preparation but increases the number of analytes. A method based on direct injection of five-fold diluted urine for confirmation of morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine, Codeine-6-Glucuronide and 6-acetylmorphine was validated using LC-MS/MS in positive electrospray mode monitoring two transitions using selected reaction monitoring. The method was applied for the analysis of 3155 unknown urine samples which were positive for opiates in immunochemical screening. A linear response was observed for all compounds in the calibration curves covering more than three orders of magnitude. Cut off was set to 2 ng/ml for 6-acetylmorphine and 150 ng/ml for the other analytes. 6-Acetylmorphine was found to be effective (sensitivity 82%) in detecting samples as heroin intake. Morphine-3-glucuronide and Codeine-6-Glucuronide was the predominant components of total morphine and codeine, 84% and 93%, respectively. The authors have validated a robust LC-MS/MS method for rapid qualitative and quantitative analysis of opiates in urine. 6-Acetylmorphine has been demonstrated as a sensitive and important parameter for a heroin intake. A possible interpretation strategy to conclude the source of detected analytes was proposed. The method might be further developed by reducing the number of analytes to morphine-3-glucuronide, Codeine-6-Glucuronide and 6-acetylmorphine without compromising test performance. Copyright © 2013 John Wiley & Sons, Ltd.
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Direct and efficient liquid chromatographic-tandem mass spectrometric method for opiates in urine drug testing – importance of 6-acetylmorphine and reduction of analytes
Drug testing and analysis, 2013Co-Authors: Maria Andersson, Nikolai Stephanson, Tommy Terzuoli, Jonatan D. Lindh, Inger Öhman, Olof BeckAbstract:Opiates comprise a class of abused drugs that is of primary interest in clinical and forensic urine drug testing. Determination of heroin, codeine, or a multi-drug ingestion is complicated since both heroin and codeine can lead to urinary excretion of free and conjugated morphine. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) offers advantage over gas chromatography-mass spectrometry by simplifying sample preparation but increases the number of analytes. A method based on direct injection of five-fold diluted urine for confirmation of morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine, Codeine-6-Glucuronide and 6-acetylmorphine was validated using LC-MS/MS in positive electrospray mode monitoring two transitions using selected reaction monitoring. The method was applied for the analysis of 3155 unknown urine samples which were positive for opiates in immunochemical screening. A linear response was observed for all compounds in the calibration curves covering more than three orders of magnitude. Cut off was set to 2 ng/ml for 6-acetylmorphine and 150 ng/ml for the other analytes. 6-Acetylmorphine was found to be effective (sensitivity 82%) in detecting samples as heroin intake. Morphine-3-glucuronide and Codeine-6-Glucuronide was the predominant components of total morphine and codeine, 84% and 93%, respectively. The authors have validated a robust LC-MS/MS method for rapid qualitative and quantitative analysis of opiates in urine. 6-Acetylmorphine has been demonstrated as a sensitive and important parameter for a heroin intake. A possible interpretation strategy to conclude the source of detected analytes was proposed. The method might be further developed by reducing the number of analytes to morphine-3-glucuronide, Codeine-6-Glucuronide and 6-acetylmorphine without compromising test performance.
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electrospray lc ms method with solid phase extraction for accurate determination of morphine codeine and ethylmorphine glucuronides and 6 acetylmorphine in urine
Journal of Analytical Toxicology, 2007Co-Authors: J O Svensson, E. Gustavsson, Maria Andersson, Olof BeckAbstract:I human urine based on solid-phase extraction (SPE) and electrospray ionization liquid chromatography-mass spectrometry (LC-MS) was validated for use as a confirmation procedure in combination with immunochemical screening for opiates. Three deuterium-labelled analogues were used as internal standards: morphine-3- glucuronide-d3, codeine-d3, and 6-acetylmorphine-d3. Fifty- microliter aliquots of urine were prepared by SPE using 30-mg Oasis HLB cartridges. The chromatographic system consisted of a 2.0 x 100-ram C18 column and the gradient elution buffers used acetonitrile and 25 mmol/L formic acid. The protonated molecular ions were monitored in the selected ion monitoring mode together with one qualifier ion for each analyte. The variability was less than 10% at the reporting limit 30 ng/mL for 6-acetylmorphine and 300 ng/mL for the other analytes. The method was validated by comparison with a reference gas chromatographic (GC)-MS method using authentic urine samples. The two methods agreed completely regarding identified analytes, and for the quantitative results there were slightly lower levels when measuring glucuronides directly as compared to total determination after hydrolysis by GC-MS. This result was to be expected because the free compounds are not measured with the LC-MS method. This study concludes that the presented LC-MS
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Validation of direct injection electrospray LC-MS/MS for confirmation of opiates in urine drug testing
Journal of mass spectrometry : JMS, 2007Co-Authors: E. Gustavsson, Nikolai Stephanson, Maria Andersson, Olof BeckAbstract:A method based on the direct injection of diluted urine for the identification and quantification of morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine, Codeine-6-Glucuronide, ethylmorphine, ethylmorphine-6-glucuronide and 6-acetylmorphine (6AM) in human urine by electrospray ionisation liquid chromatography-tandem mass spectrometry was validated for use as a confirmation procedure in urine drug testing. Four deuterium labelled analogues were used as internal standards: morphine-3-glucuronide-D3, morphine-D3, codeine-D3 and 6AM-D3. Twenty microlitre aliquots of urine were mixed with 80 μl of the internal standard solution in autosampler vials and 10 μl was injected. The chromatographic system consisted of a 2.0 × 100 mm C18 column and the gradient elution buffers used acetonitrile and 25 mmol/l formic acid. Two product ions produced from the protonated molecular ions were monitored in the selected reaction monitoring mode. The intra- and inter-assay variability (coefficient of variation) was below 10% at higher levels for all analytes, but at the reporting limits the variation was above 20% for 6AM, morphine-3-glucuronide and Codeine-6-Glucuronide. Ion suppression occurred early after injection but did not affect the identification and quantification of the analytes in authentic samples. The method was further validated by comparison with a reference gas chromatographic-mass spectrometric method using authentic urine samples. The two methods agreed almost completely (99%) regarding the identified analytes, but for the quantitative results there were slightly lower levels when measuring glucuronides directly as compared to total determination after hydrolysis by gas chromatography-mass spectrometry. We conclude that the presented liquid chromatographic-tandem mass spectrometric method is robust and reliable, and suitable for use as a confirmation method in urine drug testing for opiates Copyright © 2007 John Wiley & Sons, Ltd.
Marilyn A Huestis - One of the best experts on this subject based on the ideXlab platform.
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lc esi ms ms analysis for the quantification of morphine codeine morphine 3 β d glucuronide morphine 6 β d glucuronide and codeine 6 β d glucuronide in human urine j mass spectrom 2005 40 1412 1416
Journal of Mass Spectrometry, 2006Co-Authors: Constance M Murphy, Marilyn A HuestisAbstract:The original article to which this Erratum refers was published in Journal of Mass Spectrometry 40, 2005, 1412–1416. Copyright © 2006 John Wiley & Sons, Ltd
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lc esi ms ms analysis for the quantification of morphine codeine morphine 3 β d glucuronide morphine 6 β d glucuronide and codeine 6 β d glucuronide in human urine
Journal of Mass Spectrometry, 2005Co-Authors: Constance M Murphy, Marilyn A HuestisAbstract:A liquid chromatographic-electrospray ionization-tandem mass spectrometric method for the quantification of the opiates morphine, codeine, and their metabolites morphine-3-b-D-glucuronide (M-3-G), morphine-6-b-D-glucuronide (M-6-G) and codeine-6-b-D-glucuronide (C-6-G) in human urine has been developed and validated. Identification and quantification were based on the following transitions: 286 to 201 and 229 for morphine, 300 to 215 and 243 for codeine, 644 to 468 for M-3-G, 462 to 286 for M-6-G, and 476 to 300 for C-6-G. Calibration by linear regression analysis utilized deuterated internal standards and a weighting factor of 1/X. The method was accurate and precise across a linear dynamic range of 25.0 to 4000.0 ng/ml. Pretreatment of urine specimens using solid phase extraction was sufficient to limit matrix suppression toless than40% for allfive analytes. Themethod proved to be suitable for thequantification of morphine, codeine, and their metabolitesin urine specimens collected from opioid-dependent participants enrolled in a methadone maintenance program. Copyright 2005 John Wiley & Sons, Ltd.
Lars Slordal - One of the best experts on this subject based on the ideXlab platform.
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post mortem levels and tissue distribution of codeine codeine 6 glucuronide norcodeine morphine and morphine glucuronides in a series of codeine related deaths
Forensic Science International, 2016Co-Authors: Joachim Frost, Trine N. Løkken, Ivar Skjåk Nordrum, Arne Helland, Lars SlordalAbstract:Abstract This article presents levels and tissue distribution of codeine, Codeine-6-Glucuronide (C6G), norcodeine, morphine and the morphine metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in post-mortem blood (peripheral and heart blood), vitreous fluid, muscle, fat and brain tissue in a series of 23 codeine-related fatalities. CYP2D6 genotype is also determined and taken into account. Quantification of codeine, C6G, norcodeine, morphine, M3G and M6G was performed with a validated solid phase extraction LC–MS method. The series comprise 19 deaths (83%) attributed to mixed drug intoxication, 4 deaths (17%) attributed to other causes of death, and no cases of unambiguous monointoxication with codeine. The typical peripheral blood concentration pattern in individual cases was C6G ≫ codeine ≫ norcodeine > morphine, and M3G > M6G > morphine. In matrices other than blood, the concentration pattern was similar, although in a less systematic fashion. Measured concentrations were generally lower in matrices other than blood, especially in brain and fat, and in particular for the glucuronides (C6G, M3G and M6G) and, to some extent, morphine. In brain tissue, the presumed active moieties morphine and M6G were both below the LLOQ (0.0080 mg/L and 0.058 mg/L, respectively) in a majority of cases. In general, there was a large variability in both measured concentrations and calculated blood/tissue concentration ratios. There was also a large variability in calculated ratios of morphine to codeine, C6G to codeine and norcodeine to codeine in all matrices, and CYP2D6 genotype was not a reliable predictor of these ratios. The different blood/tissue concentration ratios showed no systematic relationship with the post-mortem interval. No coherent degradation or formation patterns for codeine, morphine, M3G and M6G were observed upon reanalysis in peripheral blood after storage.
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A validated method for simultaneous determination of codeine, Codeine-6-Glucuronide, norcodeine, morphine, morphine-3-glucuronide and morphine-6-glucuronide in post-mortem blood, vitreous fluid, muscle, fat and brain tissue by LC-MS.
Journal of Analytical Toxicology, 2015Co-Authors: Joachim Frost, Trine N. Løkken, Wenche Rødseth Brede, Ivar Skjåk Nordrum, Solfrid Hegstad, Lars SlordalAbstract:The toxicodynamics and, to a lesser degree, toxicokinetics of the widely used opiate codeine remain a matter of controversy. To address this issue, analytical methods capable of providing reliable quantification of codeine metabolites alongside codeine concentrations are required. This article presents a validated method for simultaneous determination of codeine, codeine metabolites Codeine-6-Glucuronide (C6G), norcodeine and morphine, and morphine metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in post-mortem whole blood, vitreous fluid, muscle, fat and brain tissue by high-performance liquid chromatography mass spectrometry. Samples were prepared by solid-phase extraction. The validated ranges were 1.5–300 ng/mL for codeine, norcodeine and morphine, and 23–4,600 ng/mL for C6G, M3G and M6G, with exceptions for norcodeine in muscle (3 – 300 ng/mL), morphine in muscle, fat and brain (3–300 ng/mL) and M6G in fat (46–4,600 ng/mL). Within-run and between-run accuracy (88.1–114.1%) and precision (CV 0.6–12.7%), matrix effects (CV 0.3–13.5%) and recovery (57.8–94.1%) were validated at two concentration levels; 3 and 150 ng/mL for codeine, norcodeine and morphine, and 46 and 2,300 ng/mL for C6G, M3G and M6G. Freeze– thaw and long-term stability (6 months at 28088C) was assessed, showing no significant changes in analyte concentrations (212 to 18%). The method was applied in two authentic forensic autopsy cases implicating codeine in both therapeutic and presumably lethal concentration levels.
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Investigation of morphine and morphine glucuronide levels and cytochrome P450 isoenzyme 2D6 genotype in codeine-related deaths
Forensic Science International, 2012Co-Authors: Joachim Frost, Ivar Skjåk Nordrum, Arne Helland, Lars SlordalAbstract:Abstract Compared to morphine and morphine-6-glucuronide (M6G), codeine and its other major metabolites Codeine-6-Glucuronide and norcodeine have weak affinity to opioid μ-receptors. Analgesic effects of codeine are thus largely dependent on metabolic conversion to morphine by the polymorphic cytochrome P450 isoenzyme 2D6 (CYP2D6). How this relates to toxicity and post-mortem whole blood levels is not known. This paper presents a case series of codeine-related deaths where concentrations of morphine, M6G and morphine-3-glucuronide (M3G), as well as CYP2D6 genotype, are taken into account. Post-mortem toxicological specimens from a total of 1444 consecutive forensic autopsy cases in Central Norway were analyzed. Among these, 111 cases with detectable amounts of codeine in femoral blood were identified, of which 34 had femoral blood concentrations exceeding the TIAFT toxicity threshold of 0.3 mg/L. Autopsy records of these 34 cases were retrieved and reviewed. In the 34 reviewed cases, there was a large variability in individual morphine to codeine concentration ratios (M/C ratios), and morphine levels could not be predicted from codeine concentrations, even when CYP2D6 genotype was known. 13 cases had codeine concentrations exceeding the TIAFT threshold for possibly lethal serum concentrations (1.6 mg/L). Among these, 8 individuals had morphine concentrations below the toxic threshold according to TIAFT (0.15 mg/L). In one case, morphine as well as M6G and M3G concentrations were below the limit of detection. A comprehensive investigation of codeine-related fatalities should, in addition to a detailed case history, include quantification of morphine and morphine metabolites. CYP2D6 genotyping may be of interest in cases with unexpectedly high or low M/C ratios.
Ian R Tebbett - One of the best experts on this subject based on the ideXlab platform.
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analgesic effects of codeine 6 glucuronide after intravenous administration
European Journal of Pain, 1997Co-Authors: V. Srinivasan, Donna Wielbo, Ian R TebbettAbstract:Centrally administered codeine glucuronide has been shown to exhibit antinociceptive properties with decreased immunosuppressive effects compared to codeine. In this study, Codeine-6-Glucuronide was administered to rats, and its analgesic effect was compared to that of codeine. The concentrations of codeine and its metabolites in plasma and brain were also determined at the peak response time after administration of each compound. Receptor-binding studies with rat brain homogenates and affinity profiles were also determined. Intravenous administration of Codeine-6-Glucuronide resulted in approximately 60% of the analgesic response elicited by codeine itself. Analysis of plasma and brain showed that Codeine-6-Glucuronide is relatively stable in vivo, with only small amounts of morphine-6-glucuronide being detected in addition to unchanged Codeine-6-Glucuronide. The receptor affinity of Codeine-6-Glucuronide was similar to that of codeine. It is concluded that intravenously administered Codeine-6-Glucuronide possesses analgesic activity similar to that of codeine, and may have clinical benefit in the treatment of pain
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Analgesic and Immunomodulatory Effects of Codeine and Codeine 6-glucuronide
Pharmaceutical Research, 1996Co-Authors: Vinayak Srinivasan, Donna Wielbo, James Simpkins, Janet Karlix, Kenneth Sloan, Ian R TebbettAbstract:Purpose . The antinociceptive and immunosuppressive effects of codeine and codeine 6-glucuronide were determined in rats after intra-cerebroventricular administration. Methods . Codeine 6-glucuronide was synthesized using a modification of the Koenigs-Knorr reaction. A lipophilic intermediate formed during synthesis, methyl [codein-6-yl-2,3,4-tri-O-acetyl-β-D-glucopyranosid] uronate, was also tested. Morphine was used as a positive control to compare antinociceptive potencies of these compounds. Results . All compounds tested produced significant analgesic responses, as assessed by the tail flick model. Additionally, codeine 6-glucuronide showed significantly less immunosuppressive effects than codeine in vitro . Conclusions . We conclude that codeine 6-glucuronide and related compounds may have clinical benefit in the treatment of pain in immune compromised patients.
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analgesic and immunomodulatory effects of codeine and codeine 6 glucuronide
Pharmaceutical Research, 1996Co-Authors: Vinayak Srinivasan, Donna Wielbo, James Simpkins, Janet Karlix, Kenneth B. Sloan, Ian R TebbettAbstract:Purpose. The antinociceptive and immunosuppressive effects of codeine and codeine 6-glucuronide were determined in rats after intra-cerebroventricular administration.
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High-performance liquid chromatographic determination of morphine and its metabolites in plasma using diode-array detection.
Journal of Chromatography B: Biomedical Sciences and Applications, 1993Co-Authors: Donna Wielbo, Geetha Chari, Ian R Tebbett, R Bhat, Dharmapuri Vidyasagar, A. GulatiAbstract:An isocratic high-performance liquid chromatographic method has been developed for the determination of morphine, codeine, normorphine, morphine 3-glucuronide and morphine 6-glucuronide in plasma using a diol column and diode-array detection. Samples were extracted using solid-phase extraction with recoveries in excess of 90%. The limit of determination was 1 ng/ml for morphine, codeine and morphine 3-glucuronide, and 10 ng/ml for normorphine and morphine 6-glucuronide. Inter- and intra-day precision were better than 10%.
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High-performance liquid chromatographic determination of morphine, morphine-3-glucuronide, morphine-6-glucuronide and codeine in biological samples using multi-wavelength forward optical detection.
Journal of chromatography, 1991Co-Authors: Geetha Chari, A. Gulati, R Bhat, Ian R TebbettAbstract:An isocratic high-performance liquid chromatographic method has been developed for the determination of morphine, morphine-3-glucuronide, morphine-6-glucuronide and codeine in plasma, urine and cerebrospinal fluid. The use of an efficient solid-phase extraction procedure together with a forward optical scanning detector allows a detection limit of 500 pg/ml. The method was evaluated by examination of biological samples taken from newborn infants following the intravenous administration of morphine sulfate.