The Experts below are selected from a list of 135 Experts worldwide ranked by ideXlab platform
Pirjo M Lillsunde - One of the best experts on this subject based on the ideXlab platform.
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validated toxicological determination of 30 drugs of abuse as optimized derivatives in oral fluid by long column fast gas chromatography electron impact mass spectrometry
Journal of Mass Spectrometry, 2005Co-Authors: Teemu Gunnar, Kari Ariniemi, Pirjo M LillsundeAbstract:An analytical procedure was developed for the simultaneous sensitive identification, screening and quantitation of 30 drugs of abuse using 250 µl of human oral fluid. The method employs sequential mixed-mode solid-phase extraction (SPE), optimized derivative formation and long-column fast gas chromatography/electron impact mass spectrometry (GC/EI-MS). After sequential SPE elution, the most sensitive and stable derivatives were formed by taking careful account of the characteristics of the active functional groups and possible steric hindrances affecting derivatization chemistry. Amphetamine-type stimulant drugs were acylated with heptafluorobutyric anhydride, benzodiazepines and Δ9-tetrahydrocannabinol were silylated with N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide and benzoylecgonine, codeine, ethylmorphine, 6-monoacetylmorphine, morphine, Pholcodine, buprenorphine and norbuprenorphine with N-methyl-N-(trimethylsilyl)trifluoroacetamide. In addition, the following analytes were included: methadone, cocaine, alprazolam, midazolam, fentanyl and zolpidem. In GC separation, fast temperature ramping and high carrier gas flow-rate combined with long 30 m columns of i.d. 0.32 mm offered a reduction in analysis time and sharp peak shapes while still maintaining sufficient resolution and high sample capacity. Validated parameters including selectivity, linearity, accuracy, intra- and inter-day precision, extraction efficiency and limit of quantitation were all within required limits. In contrast to previously published methods, this single procedure is suitable for the simultaneous toxicological determination of the most common illicit drugs and benzodiazepines, and also zolpidem, in a small amount of oral fluid. Copyright © 2005 John Wiley & Sons, Ltd.
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validated toxicological determination of 30 drugs of abuse as optimized derivatives in oral fluid by long column fast gas chromatography electron impact mass spectrometry
Journal of Mass Spectrometry, 2005Co-Authors: Teemu Gunnar, Kari Ariniemi, Pirjo M LillsundeAbstract:An analytical procedure was developed for the simultaneous sensitive identification, screening and quantitation of 30 drugs of abuse using 250 µl of human oral fluid. The method employs sequential mixed-mode solid-phase extraction (SPE), optimized derivative formation and long-column fast gas chromatography/electron impact mass spectrometry (GC/EI-MS). After sequential SPE elution, the most sensitive and stable derivatives were formed by taking careful account of the characteristics of the active functional groups and possible steric hindrances affecting derivatization chemistry. Amphetamine-type stimulant drugs were acylated with heptafluorobutyric anhydride, benzodiazepines and Δ9-tetrahydrocannabinol were silylated with N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide and benzoylecgonine, codeine, ethylmorphine, 6-monoacetylmorphine, morphine, Pholcodine, buprenorphine and norbuprenorphine with N-methyl-N-(trimethylsilyl)trifluoroacetamide. In addition, the following analytes were included: methadone, cocaine, alprazolam, midazolam, fentanyl and zolpidem. In GC separation, fast temperature ramping and high carrier gas flow-rate combined with long 30 m columns of i.d. 0.32 mm offered a reduction in analysis time and sharp peak shapes while still maintaining sufficient resolution and high sample capacity. Validated parameters including selectivity, linearity, accuracy, intra- and inter-day precision, extraction efficiency and limit of quantitation were all within required limits. In contrast to previously published methods, this single procedure is suitable for the simultaneous toxicological determination of the most common illicit drugs and benzodiazepines, and also zolpidem, in a small amount of oral fluid. Copyright © 2005 John Wiley & Sons, Ltd.
Teemu Gunnar - One of the best experts on this subject based on the ideXlab platform.
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validated toxicological determination of 30 drugs of abuse as optimized derivatives in oral fluid by long column fast gas chromatography electron impact mass spectrometry
Journal of Mass Spectrometry, 2005Co-Authors: Teemu Gunnar, Kari Ariniemi, Pirjo M LillsundeAbstract:An analytical procedure was developed for the simultaneous sensitive identification, screening and quantitation of 30 drugs of abuse using 250 µl of human oral fluid. The method employs sequential mixed-mode solid-phase extraction (SPE), optimized derivative formation and long-column fast gas chromatography/electron impact mass spectrometry (GC/EI-MS). After sequential SPE elution, the most sensitive and stable derivatives were formed by taking careful account of the characteristics of the active functional groups and possible steric hindrances affecting derivatization chemistry. Amphetamine-type stimulant drugs were acylated with heptafluorobutyric anhydride, benzodiazepines and Δ9-tetrahydrocannabinol were silylated with N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide and benzoylecgonine, codeine, ethylmorphine, 6-monoacetylmorphine, morphine, Pholcodine, buprenorphine and norbuprenorphine with N-methyl-N-(trimethylsilyl)trifluoroacetamide. In addition, the following analytes were included: methadone, cocaine, alprazolam, midazolam, fentanyl and zolpidem. In GC separation, fast temperature ramping and high carrier gas flow-rate combined with long 30 m columns of i.d. 0.32 mm offered a reduction in analysis time and sharp peak shapes while still maintaining sufficient resolution and high sample capacity. Validated parameters including selectivity, linearity, accuracy, intra- and inter-day precision, extraction efficiency and limit of quantitation were all within required limits. In contrast to previously published methods, this single procedure is suitable for the simultaneous toxicological determination of the most common illicit drugs and benzodiazepines, and also zolpidem, in a small amount of oral fluid. Copyright © 2005 John Wiley & Sons, Ltd.
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validated toxicological determination of 30 drugs of abuse as optimized derivatives in oral fluid by long column fast gas chromatography electron impact mass spectrometry
Journal of Mass Spectrometry, 2005Co-Authors: Teemu Gunnar, Kari Ariniemi, Pirjo M LillsundeAbstract:An analytical procedure was developed for the simultaneous sensitive identification, screening and quantitation of 30 drugs of abuse using 250 µl of human oral fluid. The method employs sequential mixed-mode solid-phase extraction (SPE), optimized derivative formation and long-column fast gas chromatography/electron impact mass spectrometry (GC/EI-MS). After sequential SPE elution, the most sensitive and stable derivatives were formed by taking careful account of the characteristics of the active functional groups and possible steric hindrances affecting derivatization chemistry. Amphetamine-type stimulant drugs were acylated with heptafluorobutyric anhydride, benzodiazepines and Δ9-tetrahydrocannabinol were silylated with N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide and benzoylecgonine, codeine, ethylmorphine, 6-monoacetylmorphine, morphine, Pholcodine, buprenorphine and norbuprenorphine with N-methyl-N-(trimethylsilyl)trifluoroacetamide. In addition, the following analytes were included: methadone, cocaine, alprazolam, midazolam, fentanyl and zolpidem. In GC separation, fast temperature ramping and high carrier gas flow-rate combined with long 30 m columns of i.d. 0.32 mm offered a reduction in analysis time and sharp peak shapes while still maintaining sufficient resolution and high sample capacity. Validated parameters including selectivity, linearity, accuracy, intra- and inter-day precision, extraction efficiency and limit of quantitation were all within required limits. In contrast to previously published methods, this single procedure is suitable for the simultaneous toxicological determination of the most common illicit drugs and benzodiazepines, and also zolpidem, in a small amount of oral fluid. Copyright © 2005 John Wiley & Sons, Ltd.
Kari Ariniemi - One of the best experts on this subject based on the ideXlab platform.
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validated toxicological determination of 30 drugs of abuse as optimized derivatives in oral fluid by long column fast gas chromatography electron impact mass spectrometry
Journal of Mass Spectrometry, 2005Co-Authors: Teemu Gunnar, Kari Ariniemi, Pirjo M LillsundeAbstract:An analytical procedure was developed for the simultaneous sensitive identification, screening and quantitation of 30 drugs of abuse using 250 µl of human oral fluid. The method employs sequential mixed-mode solid-phase extraction (SPE), optimized derivative formation and long-column fast gas chromatography/electron impact mass spectrometry (GC/EI-MS). After sequential SPE elution, the most sensitive and stable derivatives were formed by taking careful account of the characteristics of the active functional groups and possible steric hindrances affecting derivatization chemistry. Amphetamine-type stimulant drugs were acylated with heptafluorobutyric anhydride, benzodiazepines and Δ9-tetrahydrocannabinol were silylated with N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide and benzoylecgonine, codeine, ethylmorphine, 6-monoacetylmorphine, morphine, Pholcodine, buprenorphine and norbuprenorphine with N-methyl-N-(trimethylsilyl)trifluoroacetamide. In addition, the following analytes were included: methadone, cocaine, alprazolam, midazolam, fentanyl and zolpidem. In GC separation, fast temperature ramping and high carrier gas flow-rate combined with long 30 m columns of i.d. 0.32 mm offered a reduction in analysis time and sharp peak shapes while still maintaining sufficient resolution and high sample capacity. Validated parameters including selectivity, linearity, accuracy, intra- and inter-day precision, extraction efficiency and limit of quantitation were all within required limits. In contrast to previously published methods, this single procedure is suitable for the simultaneous toxicological determination of the most common illicit drugs and benzodiazepines, and also zolpidem, in a small amount of oral fluid. Copyright © 2005 John Wiley & Sons, Ltd.
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validated toxicological determination of 30 drugs of abuse as optimized derivatives in oral fluid by long column fast gas chromatography electron impact mass spectrometry
Journal of Mass Spectrometry, 2005Co-Authors: Teemu Gunnar, Kari Ariniemi, Pirjo M LillsundeAbstract:An analytical procedure was developed for the simultaneous sensitive identification, screening and quantitation of 30 drugs of abuse using 250 µl of human oral fluid. The method employs sequential mixed-mode solid-phase extraction (SPE), optimized derivative formation and long-column fast gas chromatography/electron impact mass spectrometry (GC/EI-MS). After sequential SPE elution, the most sensitive and stable derivatives were formed by taking careful account of the characteristics of the active functional groups and possible steric hindrances affecting derivatization chemistry. Amphetamine-type stimulant drugs were acylated with heptafluorobutyric anhydride, benzodiazepines and Δ9-tetrahydrocannabinol were silylated with N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide and benzoylecgonine, codeine, ethylmorphine, 6-monoacetylmorphine, morphine, Pholcodine, buprenorphine and norbuprenorphine with N-methyl-N-(trimethylsilyl)trifluoroacetamide. In addition, the following analytes were included: methadone, cocaine, alprazolam, midazolam, fentanyl and zolpidem. In GC separation, fast temperature ramping and high carrier gas flow-rate combined with long 30 m columns of i.d. 0.32 mm offered a reduction in analysis time and sharp peak shapes while still maintaining sufficient resolution and high sample capacity. Validated parameters including selectivity, linearity, accuracy, intra- and inter-day precision, extraction efficiency and limit of quantitation were all within required limits. In contrast to previously published methods, this single procedure is suitable for the simultaneous toxicological determination of the most common illicit drugs and benzodiazepines, and also zolpidem, in a small amount of oral fluid. Copyright © 2005 John Wiley & Sons, Ltd.
Elizabeth J Phillips - One of the best experts on this subject based on the ideXlab platform.
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response to letter regarding article exploring the link between Pholcodine exposure and neuromuscular blocking agent anaphylaxis
British Journal of Clinical Pharmacology, 2014Co-Authors: Anna Brusch, R C Clarke, P R Platt, Elizabeth J PhillipsAbstract:Uyttebroek et al. [1] raise some pertinent questions regarding the utility of various testing modalities in the assessment of neuromuscular blocking agent (NMBA) hypersensitivity. In our cases, clinical history was the major assessment tool for identifying Pholcodine as the inciting agent of anaphylaxis [2]. In both patients, the temporal association between Pholcodine exposure and clinical reaction was in keeping with drug-induced anaphylaxis and no alternative causes were identified. The positive allergen-specific IgE levels to Pholcodine (ImmunoCAP Phadia, Uppsala, Sweden) were used to substantiate the high index of clinical suspicion. As mentioned in the article, skin testing to Pholcodine has limited utility because it causes wheal and flare reactions in normal control subjects. While drug provocation challenges are sometimes used to confirm allergy in situations where history and skin/allergen-specific IgE testing are ambiguous, in this circumstance this was not felt appropriate, owing to the severity of systemic reaction in both patients' index events. In one of our cases, a tramadol challenge was performed to give additional options if opiate analgesics were required, and the avoidance of codeine and its active metabolite morphine was recommended. Subsequent evaluation in both our patients was targeted toward the potential for NMBA hypersensitivity given previous studies [3–6], presented in the review, suggesting an association between Pholcodine exposure and NMBA anaphylaxis. The recommendations regarding NMBA use in both patients were based on the outcome of skin testing and allergen-specific IgE testing. As Uyttebroek et al. [1] allude to, sensitization to a drug does not always equate with clinically meaningful allergy. However, provocation challenges with various NMBAs, as a means of demonstrating patient tolerance or allergy, are not feasible. Thus, the recommendations were made on the available testing at the time of assessment. The development of basophil activation tests as an adjunct to skin testing and specific IgE testing will no doubt help in the assessment of cases of suspected drug allergy. However, these tests are currently not validated or routinely available in most centres, and sensitivity may be lacking even when cases are carefully phenotyped and selected. The cases presented demonstrate the potential for sensitization to NMBA to occur in the context of Pholcodine hypersensitivity. These case studies are reflective, at an individual patient level, of the population-based evidence cited previously [3,5,6]. We agree that consideration of whether the patients are able to tolerate opiates following true Pholcodine immediate (IgE) hypersensitivity reactions is an important practical concern, and the specific haptenated products mediating such reactions are unknown. Indeed, codeine is metabolized by the genetically polymorphic isoform CYP2D6 to the active metabolite morphine, adding additional potential variability to potential cross-reactivity and patient tolerance. However, the focus of our article [2] was on the potential association of Pholcodine exposure and NMBA allergy, and thus, the presentation of the case studies reflects this. Immunoglobulin E-mediated hypersensitivity reactions to Pholcodine and morphine are rare, and this does indeed raise important questions regarding the pathogenesis of Pholcodine sensitization and NMBA anaphylaxis. At present, the mechanisms underlying why exposure and sensitization to a substituted ammonium ion in Pholcodine can prime NMBA anaphylaxis but not result in allergy to all compounds containing similar substituted ammonium ions remain unresolved.
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exploring the link between Pholcodine exposure and neuromuscular blocking agent anaphylaxis
British Journal of Clinical Pharmacology, 2014Co-Authors: Anna Brusch, R C Clarke, P R Platt, Elizabeth J PhillipsAbstract:Neuromuscular blocking agents (NMBAs) are the most commonly implicated drugs in IgE-mediated anaphylaxis during anaesthesia that can lead to perioperative morbidity and mortality. The rate of NMBA anaphylaxis shows marked geographical variation in patients who have had no known prior exposure to NMBAs, suggesting that there may be external or environmental factors that contribute to the underlying aetiology and pathophysiology of reactions. Substituted ammonium ions are shared among NMBAs and are therefore thought to be the main allergenic determinant of this class of drugs. Substituted ammonium ions are found in a wide variety of chemical structures, including prescription medications, over-the-counter medications and common household chemicals, such as the quaternary ammonium disinfectants. Epidemiological studies have shown parallels in the consumption of Pholcodine, a nonprescription antitussive drug which contains a tertiary ammonium ion, and the incidence of NMBA anaphylaxis. This link has prompted the withdrawal of Pholcodine in some countries, with an ensuing fall in the observed rate of NMBA anaphylaxis. While such observations are compelling in their suggestion of a relationship between Pholcodine exposure and NMBA hypersensitivity, important questions remain regarding the mechanisms by which Pholcodine is able to sensitize against NMBAs and whether there are other, as yet unidentified, agents that can elicit similar hypersensitivity reactions. This review aims to explore the evidence linking Pholcodine exposure to NMBA hypersensitivity and discuss the implications for our understanding of the pathophysiology of these reactions.
Skellern G.g. - One of the best experts on this subject based on the ideXlab platform.
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Comparative biotransformation of morphine, codeine and Pholcodine in rat hepatocytes: identification of a novel metabolite of Pholcodine
2002Co-Authors: Jairaj M., Watson D.g., Grant M.h., Skellern G.g.Abstract:1. Pholcodine (3-morpholinoethylmorphine), a semi-synthetic alkaloid, is widely used as an antitussive agent. 2. NorPholcodine [7,8-didehydro-4,5alpha-epoxy-3-(2-morpholinoethoxy)morphinan-6alpha-ol] (NP) and Pholcodine-N-oxide [1(9a)-dehydro-(4aR,5S,7aR,9cS,12S)-4a,5,7a,8,9,9a-hexahydro-5-hydroxy-12-methyl-3-morpholinoethoxy-1H-8,9,c-(iminoethano)phenanthro[4,5-bcd] furan-12-oxide] (PNOX) were identified in incubations of Pholcodine with freshly isolated rat hepatocytes by liquid chromatography/electrospray-mass spectrometry (LC/ESI-MS). 3. Synthesized NP and PNOX were characterized by mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. 4. N-oxidation was the major metabolic pathway for Pholcodine, producing a previously unreported metabolite. 5. The metabolism of morphine and codeine was also determined using freshly isolated hepatocytes. 6. For morphine, 3-glucuronidation was the major metabolic pathway, whilst for codeine it was dealkylation (O- and N-). 7. Neither morphine nor its metabolites were metabolites of Pholcodine. 8. This observation supports the hypothesis that the absence of analgesic activity with Pholcodine may be due to less O-dealkylation in vivo. 9. Together with the slow biotransformation of Pholcodine (k(met) = 0.021 microM min(-1)) in comparison with morphine (k(met) = 0.057 microM min(-1)) and codeine (k(met) = 0.112 microM min(-1)), the results obtained were consistent with its low addiction potential and suggest that its antitussive efficacy is mediated by the parent drug or one of its metabolites other than morphine
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Metabolic profiling of the antitussive drug Pholcodine in rat hepatocytes
2002Co-Authors: Jairaj M., Watson D.g., Grant M.h., Skellern G.g.Abstract:This paper looks at metabolic profiling of the antitussive drug Pholcodine in rat hepatocyte
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Identification of metabolites of Pholcodine by lC/MS
2001Co-Authors: Jairaj M., Watson D.g., Grant M.h., Skellern G.g.Abstract:This paper looks at the identification of metabolites of Pholcodine by lC/M
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Study of the in vitro metabolism of the antitussive Pholcodine: metabolic profiling and pharmacokinetics in isolated rat hepatocytes
Pharmaceutical Press, 2001Co-Authors: Jairaj M., Watson D.g., Skellern G.g., Grant M.h.Abstract:Conference paper discussing a study of the in vitro metabolism of the antitussive Pholcodine: metabolic profiling and pharmacokinetics in isolated rat hepatocytes
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Metabolic profiling of the antitissive Pholcodine in rat hepatocytes : identification of a novel metabolite by lC/+ESI- mS
2001Co-Authors: Jairaj M., Watson D.g., Grant M.h., Skellern G.g.Abstract:This paper looks at metabolic profiling of the antitissive Pholcodine in rat hepatocytes and the identification of a novel metabolite by lC/+ESI- m