The Experts below are selected from a list of 231 Experts worldwide ranked by ideXlab platform
Hans Bundgaard - One of the best experts on this subject based on the ideXlab platform.
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enhanced delivery of Ketobemidone through porcine buccal mucosa in vitro via more lipophilic ester prodrugs
International Journal of Pharmaceutics, 1992Co-Authors: Laila Bach Hansen, Lona L. Christrup, Hans BundgaardAbstract:The in vitro penetration of Ketobemidone and various ester prodrugs through porcine buccal mucosa in a modified Ussing chamber was investigated in order to support the selection of a prodrug derivative with optimal buccal absorption. The nine esters studied included carboxylic acid and carbonate esters formed at the phenolic hydroxy group of Ketobemidone. The esters were all rapidly hydrolyzed to the parent drug in a porcine buccal epithelial homogenate and only free Ketobemidone was detected in the receptor compartment of the Ussing chamber. All the ester prodrugs showed enhanced rates of permeation relative to Ketobemidone, the permeability coefficients being 3–30-times higher than that of Ketobemidone. The permeability coefficients increased with increasing lipophilicity, expressed in terms of octanol-buffer (pH 7.4) partition coefficients (P), up to log P values of about 1.5 whereupon a plateau or a slight decrease occurred. No toxic effects of Ketobemidone or the prodrugs on the buccal membrane were observed as judged from monitoring of the electrical properties of the membrane.
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buccal absorption of Ketobemidone and various ester prodrugs in the rat
International Journal of Pharmaceutics, 1992Co-Authors: Laila Bach Hansen, Lona L. Christrup, Aksel Jorgensen, Soren N Rasmussen, Hans BundgaardAbstract:Abstract The buccal absorption of Ketobemidone, a strong narcotic analgesic, and various carboxylate and carbonate ester prodrugs was studied in rats. The compounds were administered in the form of aqueous solutions of pH 7.4. The absolute bioavailability of Ketobemidone following buccal dosing was 26% whereas the bioavailability of Ketobemidone following buccal administration of the prodrugs ranged from 37 to 98%. The highest bioavailability was obtained with the ethyl carbonate ester. An apparent parabolic correlation between bioavailability and lipophilicity of the compounds was seen. All esters were rapidly hydrolyzed to Ketobemidone after both buccal and intravenous administration. The acute toxicity of the esters after i.v. administration to mice and rats was similar to that of the parent drug. It is concluded that esterification of the phenolic hydroxyl group in Ketobemidone to give a more lipophilic prodrug may be a useful approach to improve the buccal delivery of this analgesic.
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Ketobemidone prodrugs for buccal delivery prediction of the extent of saliva catalyzed hydrolysis of various ester prodrugs under simulated in vivo conditions
International Journal of Pharmaceutics, 1992Co-Authors: Laila Bach Hansen, Lona L. Christrup, Hans BundgaardAbstract:Abstract As part of studies aiming at developing a Ketobemidone prodrug suitable for buccal or sublingual administration, the potential impact of saliva enzyme-catalyzed hydrolysis of various ester prodrugs was assessed. The hydrolysis of three Ketobemidone esters in human whole saliva, obtained under conditions ensuring maximal esterase activity, was studied as a function of ester concentration at 37°C. The kinetics of hydrolysis could be accounted for in terms of the Michaelis-Menten equation and the rate parameters Km and Vmax were determined. Due to the occurrence of zero-order kinetics at pharmacologically relevant prodrug concentrations, degradation of the esters by saliva enzymes was predicted to occur to only a minor extent (1–6%) under conditions similar to those prevailing in vivo after administration of buccal or sublingual tablets of the esters. The mode of administration of tablets for use in the mouth and their rate of disintegration were shown to have some influence on the rate of saliva secretion and hence on saliva esterase activity but not to an extent compromising the efficient buccal or sublingual delivery of the Ketobemidone prodrugs.
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saliva catalyzed hydrolysis of a Ketobemidone ester prodrug factors influencing human salivary esterase activity
International Journal of Pharmaceutics, 1992Co-Authors: Laila Bach Hansen, Lona L. Christrup, Hans BundgaardAbstract:Abstract Saliva enzyme-catalysed hydrolysis of ester prodrugs containing sensitive ester groups may be a limiting factor to the buccal absorption of such compounds. Using the isopropyl carbonate ester of Ketobemidone as a model substance of a hydrolysis-sensitive prodrug the esterase activity of human saliva has been characterized as a function of various factors. The esterase activity was found to decrease rapidly upon storage of the saliva at 37°C. The activity increased with increasing pH in the range 4.5–7.4 and with increasing salivation flow rate up to a rate of 0.9 ml min −1 . Under resting conditions, the flow rate was about 0.2 ml min −1 which implied a greatly decreased esterase activity. The activity was highest after fasting and decreased after intake of a meal. The intraindividual variation in the saliva esterase activity was small whereas a larger interindividual variation was found.
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Enhanced transdermal delivery of Ketobemidone with prodrugs
International Journal of Pharmaceutics, 1992Co-Authors: Laila Bach Hansen, Ann Fullerton, Lona L. Christrup, Hans BundgaardAbstract:Abstract The feasibility of achieving transdermal delivery of the opioid analgesic kelobemidone was assessed in human skin penetration studies in vitro using both Ketobemidone itself and three carbonate ester prodrugs formed at the phenolic hydroxyl group. Whereas Ketobemidone itself only showed a limited ability to permeate the skin from either polar or apolar vehicles the ester prodrugs very readily penetrated through the skin from solutions in isopropyi myristate and, in particular, from ethanol and ethanol-water solutions. Thus. steady-state fluxes in the range of 40–140 μg Ketobemidone base cm 2 per h were observed for the Ketobemidone esters from 20% w/v solutions in ethanol and ethanol-water (3:1 and 1: 1 v/v) vehicles. The esters were rapidly hydrolyzed to the parent drug in the presence of skin enzymes and only free Ketobemidone was detected in the receptor phase. The study demonstrates the feasibility of achieving transdermal delivery of ketohemidone based on the ready enzymatic conversion and the favourable skin penetration properties of the ester prodrugs which in turn are attributed to their high solubilities in both polar and apolar solvents.
Per E Andren - One of the best experts on this subject based on the ideXlab platform.
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in vivo investigation of brain and systemic Ketobemidone metabolism
Analyst, 2010Co-Authors: Ingela Sundstrom, Joris Arts, Douglas Westerlund, Per E AndrenAbstract:Ketobemidone metabolites have previously been identified in urine and plasma; here we show, for the first time, that norKetobemidone and Ketobemidone N-oxide are present in in vivo microdialysate from rat brain (striatum) after reverse microdialysis, suggesting striatal metabolism of Ketobemidone. Ketobemidone metabolites were also identified in in vivo microdialysate samples from brain and blood, as well as in urine from rats, after subcutaneous administration of Ketobemidone. Three Phase I metabolites (norKetobemidone, Ketobemidone N-oxide and hydroxymethoxyKetobemidone) and three Phase II metabolites (glucuronic acid conjugates of Ketobemidone, norKetobemidone and hydroxymethoxyKetobemidone) were identified in the microdialysates after subcutaneous administration. Coupled capillary liquid chromatography tandem mass spectrometry (LC-MS/MS) and SPE (boronate)-MS/MS were utilized for the analysis of the biological samples. The Phase I metabolites were identified by comparing the retention times and tandem mass spectra of the microdialysates with synthetic standards. The Phase II metabolites were identified by determination of exact masses and by comparing the tandem mass spectra of the microdialysates with those of synthetic standards for the aglycones. HydroxyKetobemidone, a catechol-type Phase I metabolite, was selectively isolated by solid-phase boronate-complexation but identified in urine alone. This work demonstrated that the in vivo microdialysis technique in combination with LC-MS/MS can be used to study the local metabolism of a drug in the brain.
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method development for identification of Ketobemidone metabolites in microdialysate samples by coupled column capillary liquid chromatography tandem mass spectrometry
Journal of Chromatography A, 2008Co-Authors: Ingela Sundstrom, Per E Andren, Douglas WesterlundAbstract:Abstract Methodologies for identification of Ketobemidone metabolites in microdialysate samples utilizing coupled-column capillary liquid chromatography–electrospray quadrupole time-of-flight tandem mass spectrometry are presented. Two different methods were developed to efficiently analyze the metabolites norKetobemidone, Ketobemidone N -oxide and hydroxyKetobemidone, respectively. Both methods include on-line desalting and trapping of the analytes on micro-solid-phase extraction columns with different retention mechanisms. NorKetobemidone and Ketobemidone N -oxide were trapped on a C18 column and then eluted by back-flush followed by isocratic separation on a fluorinated reversed-phase type silica gel column (Fluofix). Retention equations are proposed for the chromatographic observations made on the Fluofix column. HydroxyKetobemidone was trapped on a phenylboronic acid column by complex formation at basic pH and then eluted at acidic pH directly into to the mass spectrometer. Oxidation of hydroxyKetobemidone to its corresponding quinone was also observed. The methods were successfully used to analyze synthetic Ketobemidone metabolites in dilute low-volume microdialysis samples.
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Method development for identification of Ketobemidone metabolites in microdialysate samples by coupled-column capillary liquid chromatography–tandem mass spectrometry
Journal of Chromatography A, 2008Co-Authors: Ingela Sundstrom, Per E Andren, Douglas WesterlundAbstract:Abstract Methodologies for identification of Ketobemidone metabolites in microdialysate samples utilizing coupled-column capillary liquid chromatography–electrospray quadrupole time-of-flight tandem mass spectrometry are presented. Two different methods were developed to efficiently analyze the metabolites norKetobemidone, Ketobemidone N-oxide and hydroxyKetobemidone, respectively. Both methods include on-line desalting and trapping of the analytes on micro-solid-phase extraction columns with different retention mechanisms. NorKetobemidone and Ketobemidone N-oxide were trapped on a C18 column and then eluted by back-flush followed by isocratic separation on a fluorinated reversed-phase type silica gel column (Fluofix). Retention equations are proposed for the chromatographic observations made on the Fluofix column. HydroxyKetobemidone was trapped on a phenylboronic acid column by complex formation at basic pH and then eluted at acidic pH directly into to the mass spectrometer. Oxidation of hydroxyKetobemidone to its corresponding quinone was also observed. The methods were successfully used to analyze synthetic Ketobemidone metabolites in dilute low-volume microdialysis samples.
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identification of Ketobemidone metabolites by capillary lc ms ms part ii identification of Ketobemidone metabolites in rat blood and brain in vivo microdialysates and urine
2004Co-Authors: Ingela Sundstrom, Joris Arts, Douglas Westerlund, Per E AndrenAbstract:Identification of Ketobemidone metabolites by capillary LC-MS/MS : Part II: Identification of Ketobemidone metabolites in rat blood and brain in vivo microdialysates and urine
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identification of Ketobemidone metabolites by capillary lc ms ms part i method development for analysis of in vivo micro dialysates
2004Co-Authors: Ingela Sundstrom, Per E Andren, Douglas WesterlundAbstract:Identification of Ketobemidone metabolites by capillary LC-MS/MS : Part I: Method development for analysis of in vivo micro-dialysates
Laila Bach Hansen - One of the best experts on this subject based on the ideXlab platform.
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enhanced delivery of Ketobemidone through porcine buccal mucosa in vitro via more lipophilic ester prodrugs
International Journal of Pharmaceutics, 1992Co-Authors: Laila Bach Hansen, Lona L. Christrup, Hans BundgaardAbstract:The in vitro penetration of Ketobemidone and various ester prodrugs through porcine buccal mucosa in a modified Ussing chamber was investigated in order to support the selection of a prodrug derivative with optimal buccal absorption. The nine esters studied included carboxylic acid and carbonate esters formed at the phenolic hydroxy group of Ketobemidone. The esters were all rapidly hydrolyzed to the parent drug in a porcine buccal epithelial homogenate and only free Ketobemidone was detected in the receptor compartment of the Ussing chamber. All the ester prodrugs showed enhanced rates of permeation relative to Ketobemidone, the permeability coefficients being 3–30-times higher than that of Ketobemidone. The permeability coefficients increased with increasing lipophilicity, expressed in terms of octanol-buffer (pH 7.4) partition coefficients (P), up to log P values of about 1.5 whereupon a plateau or a slight decrease occurred. No toxic effects of Ketobemidone or the prodrugs on the buccal membrane were observed as judged from monitoring of the electrical properties of the membrane.
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buccal absorption of Ketobemidone and various ester prodrugs in the rat
International Journal of Pharmaceutics, 1992Co-Authors: Laila Bach Hansen, Lona L. Christrup, Aksel Jorgensen, Soren N Rasmussen, Hans BundgaardAbstract:Abstract The buccal absorption of Ketobemidone, a strong narcotic analgesic, and various carboxylate and carbonate ester prodrugs was studied in rats. The compounds were administered in the form of aqueous solutions of pH 7.4. The absolute bioavailability of Ketobemidone following buccal dosing was 26% whereas the bioavailability of Ketobemidone following buccal administration of the prodrugs ranged from 37 to 98%. The highest bioavailability was obtained with the ethyl carbonate ester. An apparent parabolic correlation between bioavailability and lipophilicity of the compounds was seen. All esters were rapidly hydrolyzed to Ketobemidone after both buccal and intravenous administration. The acute toxicity of the esters after i.v. administration to mice and rats was similar to that of the parent drug. It is concluded that esterification of the phenolic hydroxyl group in Ketobemidone to give a more lipophilic prodrug may be a useful approach to improve the buccal delivery of this analgesic.
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Ketobemidone prodrugs for buccal delivery prediction of the extent of saliva catalyzed hydrolysis of various ester prodrugs under simulated in vivo conditions
International Journal of Pharmaceutics, 1992Co-Authors: Laila Bach Hansen, Lona L. Christrup, Hans BundgaardAbstract:Abstract As part of studies aiming at developing a Ketobemidone prodrug suitable for buccal or sublingual administration, the potential impact of saliva enzyme-catalyzed hydrolysis of various ester prodrugs was assessed. The hydrolysis of three Ketobemidone esters in human whole saliva, obtained under conditions ensuring maximal esterase activity, was studied as a function of ester concentration at 37°C. The kinetics of hydrolysis could be accounted for in terms of the Michaelis-Menten equation and the rate parameters Km and Vmax were determined. Due to the occurrence of zero-order kinetics at pharmacologically relevant prodrug concentrations, degradation of the esters by saliva enzymes was predicted to occur to only a minor extent (1–6%) under conditions similar to those prevailing in vivo after administration of buccal or sublingual tablets of the esters. The mode of administration of tablets for use in the mouth and their rate of disintegration were shown to have some influence on the rate of saliva secretion and hence on saliva esterase activity but not to an extent compromising the efficient buccal or sublingual delivery of the Ketobemidone prodrugs.
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saliva catalyzed hydrolysis of a Ketobemidone ester prodrug factors influencing human salivary esterase activity
International Journal of Pharmaceutics, 1992Co-Authors: Laila Bach Hansen, Lona L. Christrup, Hans BundgaardAbstract:Abstract Saliva enzyme-catalysed hydrolysis of ester prodrugs containing sensitive ester groups may be a limiting factor to the buccal absorption of such compounds. Using the isopropyl carbonate ester of Ketobemidone as a model substance of a hydrolysis-sensitive prodrug the esterase activity of human saliva has been characterized as a function of various factors. The esterase activity was found to decrease rapidly upon storage of the saliva at 37°C. The activity increased with increasing pH in the range 4.5–7.4 and with increasing salivation flow rate up to a rate of 0.9 ml min −1 . Under resting conditions, the flow rate was about 0.2 ml min −1 which implied a greatly decreased esterase activity. The activity was highest after fasting and decreased after intake of a meal. The intraindividual variation in the saliva esterase activity was small whereas a larger interindividual variation was found.
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Enhanced transdermal delivery of Ketobemidone with prodrugs
International Journal of Pharmaceutics, 1992Co-Authors: Laila Bach Hansen, Ann Fullerton, Lona L. Christrup, Hans BundgaardAbstract:Abstract The feasibility of achieving transdermal delivery of the opioid analgesic kelobemidone was assessed in human skin penetration studies in vitro using both Ketobemidone itself and three carbonate ester prodrugs formed at the phenolic hydroxyl group. Whereas Ketobemidone itself only showed a limited ability to permeate the skin from either polar or apolar vehicles the ester prodrugs very readily penetrated through the skin from solutions in isopropyi myristate and, in particular, from ethanol and ethanol-water solutions. Thus. steady-state fluxes in the range of 40–140 μg Ketobemidone base cm 2 per h were observed for the Ketobemidone esters from 20% w/v solutions in ethanol and ethanol-water (3:1 and 1: 1 v/v) vehicles. The esters were rapidly hydrolyzed to the parent drug in the presence of skin enzymes and only free Ketobemidone was detected in the receptor phase. The study demonstrates the feasibility of achieving transdermal delivery of ketohemidone based on the ready enzymatic conversion and the favourable skin penetration properties of the ester prodrugs which in turn are attributed to their high solubilities in both polar and apolar solvents.
Mikael Hedeland - One of the best experts on this subject based on the ideXlab platform.
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validation of a method for quantification of Ketobemidone in human plasma with liquid chromatography tandem mass spectrometry
Journal of Chromatography B, 2003Co-Authors: Matilda Lampinen, Ulf Bondesson, Elisabeth Fredriksson, Mikael HedelandAbstract:Abstract A liquid chromatography tandem mass spectrometry (LC–MS–MS) method for determination of the analgesic aminophenol Ketobemidone in human plasma is presented. Two preparation methods for plasma samples containing Ketobemidone were compared, liquid–liquid extraction (LLE) and solid-phase extraction (SPE). Both methods showed good precision ( n =10), 1.7% and 2.9%, respectively (0.04 μ M ) and 1.1% and 2.5%, respectively (0.14 μ M ). The accuracy was 98% and 103%, respectively (0.04 μ M ) and 105% and 99%, respectively (0.14 μ M ). Ketobemidone could be quantified at 0.43 n M , with a relative standard deviation of 17.5% ( n =19) using LLE and 18.6% ( n =10) using SPE. This level was an order of magnitude lower than earlier reported quantification limits. Quantitative data from plasma samples analyzed with LC–MS–MS were in good agreement with those obtained by gas chromatography with chemical ionization mass spectrometry (GC-CI/MS). This indicates that LC–MS–MS is a good alternative method to GC–MS as it is more sensitive and time-consuming derivatization can be avoided.
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Validation of a method for quantification of Ketobemidone in human plasma with liquid chromatography–tandem mass spectrometry
Journal of Chromatography B, 2003Co-Authors: Matilda Lampinen, Ulf Bondesson, Elisabeth Fredriksson, Mikael HedelandAbstract:Abstract A liquid chromatography tandem mass spectrometry (LC–MS–MS) method for determination of the analgesic aminophenol Ketobemidone in human plasma is presented. Two preparation methods for plasma samples containing Ketobemidone were compared, liquid–liquid extraction (LLE) and solid-phase extraction (SPE). Both methods showed good precision (n=10), 1.7% and 2.9%, respectively (0.04 μM) and 1.1% and 2.5%, respectively (0.14 μM). The accuracy was 98% and 103%, respectively (0.04 μM) and 105% and 99%, respectively (0.14 μM). Ketobemidone could be quantified at 0.43 nM, with a relative standard deviation of 17.5% (n=19) using LLE and 18.6% (n=10) using SPE. This level was an order of magnitude lower than earlier reported quantification limits. Quantitative data from plasma samples analyzed with LC–MS–MS were in good agreement with those obtained by gas chromatography with chemical ionization mass spectrometry (GC-CI/MS). This indicates that LC–MS–MS is a good alternative method to GC–MS as it is more sensitive and time-consuming derivatization can be avoided.
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identification of glucuronide conjugates of Ketobemidone and its phase i metabolites in human urine utilizing accurate mass and tandem time of flight mass spectrometry
Journal of Mass Spectrometry, 2002Co-Authors: Ingela Sundstrom, Ulf Bondesson, Per E Andren, Mikael HedelandAbstract:Identification of glucuronide conjugates of Ketobemidone and its phase I metabolites in human urine utilizing accurate mass and tandem time-of-flight mass spectrometry
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identification of phase i and phase ii metabolites of Ketobemidone in patient urine using liquid chromatography electrospray tandem mass spectrometry
Journal of Chromatography B: Biomedical Sciences and Applications, 2001Co-Authors: Ingela Sundstrom, Ulf Bondesson, Mikael HedelandAbstract:Abstract Ketobemidone and five of its phase I metabolites were identified in the urine of four patients post intravenous administration of Ketogan Novum®. Furthermore, indications of the presence of the glucuronide conjugates of Ketobemidone and norKetobemidone is presented. Both hydrolyzed (β-glucuronidase) and unhydrolyzed human urine was extracted on a mixed-mode slightly polar cation-exchange SPEC cartridge prior to analysis with LC–ESI-MS–MS. The phase I metabolites were identified by comparison of their daughter spectra with those of synthesized standards. The glucuronides were identified by their molecular mass and interpretation of the daughter spectra, as no standards were available for these compounds.
Ingela Sundstrom - One of the best experts on this subject based on the ideXlab platform.
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in vivo investigation of brain and systemic Ketobemidone metabolism
Analyst, 2010Co-Authors: Ingela Sundstrom, Joris Arts, Douglas Westerlund, Per E AndrenAbstract:Ketobemidone metabolites have previously been identified in urine and plasma; here we show, for the first time, that norKetobemidone and Ketobemidone N-oxide are present in in vivo microdialysate from rat brain (striatum) after reverse microdialysis, suggesting striatal metabolism of Ketobemidone. Ketobemidone metabolites were also identified in in vivo microdialysate samples from brain and blood, as well as in urine from rats, after subcutaneous administration of Ketobemidone. Three Phase I metabolites (norKetobemidone, Ketobemidone N-oxide and hydroxymethoxyKetobemidone) and three Phase II metabolites (glucuronic acid conjugates of Ketobemidone, norKetobemidone and hydroxymethoxyKetobemidone) were identified in the microdialysates after subcutaneous administration. Coupled capillary liquid chromatography tandem mass spectrometry (LC-MS/MS) and SPE (boronate)-MS/MS were utilized for the analysis of the biological samples. The Phase I metabolites were identified by comparing the retention times and tandem mass spectra of the microdialysates with synthetic standards. The Phase II metabolites were identified by determination of exact masses and by comparing the tandem mass spectra of the microdialysates with those of synthetic standards for the aglycones. HydroxyKetobemidone, a catechol-type Phase I metabolite, was selectively isolated by solid-phase boronate-complexation but identified in urine alone. This work demonstrated that the in vivo microdialysis technique in combination with LC-MS/MS can be used to study the local metabolism of a drug in the brain.
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method development for identification of Ketobemidone metabolites in microdialysate samples by coupled column capillary liquid chromatography tandem mass spectrometry
Journal of Chromatography A, 2008Co-Authors: Ingela Sundstrom, Per E Andren, Douglas WesterlundAbstract:Abstract Methodologies for identification of Ketobemidone metabolites in microdialysate samples utilizing coupled-column capillary liquid chromatography–electrospray quadrupole time-of-flight tandem mass spectrometry are presented. Two different methods were developed to efficiently analyze the metabolites norKetobemidone, Ketobemidone N -oxide and hydroxyKetobemidone, respectively. Both methods include on-line desalting and trapping of the analytes on micro-solid-phase extraction columns with different retention mechanisms. NorKetobemidone and Ketobemidone N -oxide were trapped on a C18 column and then eluted by back-flush followed by isocratic separation on a fluorinated reversed-phase type silica gel column (Fluofix). Retention equations are proposed for the chromatographic observations made on the Fluofix column. HydroxyKetobemidone was trapped on a phenylboronic acid column by complex formation at basic pH and then eluted at acidic pH directly into to the mass spectrometer. Oxidation of hydroxyKetobemidone to its corresponding quinone was also observed. The methods were successfully used to analyze synthetic Ketobemidone metabolites in dilute low-volume microdialysis samples.
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Method development for identification of Ketobemidone metabolites in microdialysate samples by coupled-column capillary liquid chromatography–tandem mass spectrometry
Journal of Chromatography A, 2008Co-Authors: Ingela Sundstrom, Per E Andren, Douglas WesterlundAbstract:Abstract Methodologies for identification of Ketobemidone metabolites in microdialysate samples utilizing coupled-column capillary liquid chromatography–electrospray quadrupole time-of-flight tandem mass spectrometry are presented. Two different methods were developed to efficiently analyze the metabolites norKetobemidone, Ketobemidone N-oxide and hydroxyKetobemidone, respectively. Both methods include on-line desalting and trapping of the analytes on micro-solid-phase extraction columns with different retention mechanisms. NorKetobemidone and Ketobemidone N-oxide were trapped on a C18 column and then eluted by back-flush followed by isocratic separation on a fluorinated reversed-phase type silica gel column (Fluofix). Retention equations are proposed for the chromatographic observations made on the Fluofix column. HydroxyKetobemidone was trapped on a phenylboronic acid column by complex formation at basic pH and then eluted at acidic pH directly into to the mass spectrometer. Oxidation of hydroxyKetobemidone to its corresponding quinone was also observed. The methods were successfully used to analyze synthetic Ketobemidone metabolites in dilute low-volume microdialysis samples.
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identification of Ketobemidone metabolites by capillary lc ms ms part ii identification of Ketobemidone metabolites in rat blood and brain in vivo microdialysates and urine
2004Co-Authors: Ingela Sundstrom, Joris Arts, Douglas Westerlund, Per E AndrenAbstract:Identification of Ketobemidone metabolites by capillary LC-MS/MS : Part II: Identification of Ketobemidone metabolites in rat blood and brain in vivo microdialysates and urine
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identification of Ketobemidone metabolites by capillary lc ms ms part i method development for analysis of in vivo micro dialysates
2004Co-Authors: Ingela Sundstrom, Per E Andren, Douglas WesterlundAbstract:Identification of Ketobemidone metabolites by capillary LC-MS/MS : Part I: Method development for analysis of in vivo micro-dialysates
