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Investigation of ex vivo stability of fesoterodine in human plasma and its simultaneous determination together with its active metabolite 5-HMT by LC–ESI-MS/MS: Application to a bioequivalence study
08 January 2013,
02:17:56
15 January 2013
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
Fesoterodine is a non-selective muscarinic-receptor antagonist, used in the treatment of overactive bladder syndrome. A highly sensitive, selective and rapid method has been developed for the simultaneous determination of fesoterodine and its active metabolite, 5-hydroxymethyl tolterodine (5-HMT) in human plasma by liquid chromatography–tandem mass spectrometry (LC–ESI-MS/MS). Due to rapid conversion of parent drug to 5-HMT, ex vivo stability of fesoterodine in human plasma was extensively studied to optimize the extraction protocol. The analytes and their deuterated analogs were quantitatively extracted from 100μL human plasma by liquid–liquid extraction in methyl tert-butyl ether: n-hexane. The chromatographic separation of analytes was achieved on a Kromasil C18 (100mm×4.6mm, 5μm) column under isocratic conditions. The method was validated over a dynamic concentration range of 0.01–10ng/mL for both the analytes. Ion-suppression effects were investigated by post-column infusion of analytes. The precision (% CV) values for the calculated slopes of calibration curves, which would reflect the relative matrix effect, were less than 1.5% for both the analytes. The intra-batch and inter-batch precision (% CV) across quality control levels varied from 1.82 to 3.73% and the mean extraction recovery was >96% for both the analytes. The method was successfully applied to a bioequivalence study of 8mg fesoterodine tablet formulation (test and reference) in 12 healthy Indian subjects under fasted and fed condition. The assay reproducibility estimated by reanalysis of incurred samples showed a change of ±12.0%.
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
Fesoterodine is a non-selective muscarinic-receptor antagonist, used in the treatment of overactive bladder syndrome. A highly sensitive, selective and rapid method has been developed for the simultaneous determination of fesoterodine and its active metabolite, 5-hydroxymethyl tolterodine (5-HMT) in human plasma by liquid chromatography–tandem mass spectrometry (LC–ESI-MS/MS). Due to rapid conversion of parent drug to 5-HMT, ex vivo stability of fesoterodine in human plasma was extensively studied to optimize the extraction protocol. The analytes and their deuterated analogs were quantitatively extracted from 100μL human plasma by liquid–liquid extraction in methyl tert-butyl ether: n-hexane. The chromatographic separation of analytes was achieved on a Kromasil C18 (100mm×4.6mm, 5μm) column under isocratic conditions. The method was validated over a dynamic concentration range of 0.01–10ng/mL for both the analytes. Ion-suppression effects were investigated by post-column infusion of analytes. The precision (% CV) values for the calculated slopes of calibration curves, which would reflect the relative matrix effect, were less than 1.5% for both the analytes. The intra-batch and inter-batch precision (% CV) across quality control levels varied from 1.82 to 3.73% and the mean extraction recovery was >96% for both the analytes. The method was successfully applied to a bioequivalence study of 8mg fesoterodine tablet formulation (test and reference) in 12 healthy Indian subjects under fasted and fed condition. The assay reproducibility estimated by reanalysis of incurred samples showed a change of ±12.0%.
Highlights
► First report on simultaneous determination of FESO and 5-HMT in human plasma. ► Thorough investigation of ex vivo stability of fesoterodine in plasma samples. ► Mitigation of FESO degradation by pre-treatment of blood with sodium metabisulphite. ► The method is practically free of endogenous/exogenous matrix interference. ► Bioequivalence study in healthy Indian volunteers and incurred sample reanalysis.Rapid determination of letrozole, citalopram and their metabolites by high performance liquid chromatography-fluorescence detection in urine: Method validation and application to real samples
08 January 2013,
02:17:56
15 January 2013
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
This work reports the validation of a high precision and accuracy method for the simultaneous determination of letrozole, citalopram and their metabolites in urine by high performance liquid chromatography with fluorescence detection. Dilution (urine:mobile phase, 1:2, v/v) was the only sample preparation step. The separation was carried out in a Kromasil C18 (150mm×4.6mm) column, and the mobile phase was phosphate buffer 80mM (pH 3.0) and acetonitrile (65:35, v/v) at a flow rate of 1.0mL/min. The analytes were detected at 295nm after excitation at 230nm. Linearity was observed in the range of 1.0–1000ng/mL for letrozole and its metabolite and 2.5–1000ng/mL for citalopram and their metabolites, with limits of detection and quantification between 0.09–1.0 and 0.27–1.65ng/mL, respectively. The precisions were satisfactory with RSDs between 0.17 and 5.71%. The accuracy was studied by spiking three urines from healthy female volunteers, and the recoveries were from 85 to 103%. The method was applied to urine samples from women under treatment for breast cancer and depression diseases.
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
This work reports the validation of a high precision and accuracy method for the simultaneous determination of letrozole, citalopram and their metabolites in urine by high performance liquid chromatography with fluorescence detection. Dilution (urine:mobile phase, 1:2, v/v) was the only sample preparation step. The separation was carried out in a Kromasil C18 (150mm×4.6mm) column, and the mobile phase was phosphate buffer 80mM (pH 3.0) and acetonitrile (65:35, v/v) at a flow rate of 1.0mL/min. The analytes were detected at 295nm after excitation at 230nm. Linearity was observed in the range of 1.0–1000ng/mL for letrozole and its metabolite and 2.5–1000ng/mL for citalopram and their metabolites, with limits of detection and quantification between 0.09–1.0 and 0.27–1.65ng/mL, respectively. The precisions were satisfactory with RSDs between 0.17 and 5.71%. The accuracy was studied by spiking three urines from healthy female volunteers, and the recoveries were from 85 to 103%. The method was applied to urine samples from women under treatment for breast cancer and depression diseases.
Highlights
► This report describes the validation of an high precision and accuracy HPLC-fluorescence method for the simultaneous determination of letrozole, citralopram and their metabolites in human urine. ► This method was applied to the analysis of human urine samples from cancer patients. ► The method was performed using a urine sample with only a dilution step 1:2.Determination of 5-HT receptor antagonists, MEFWAY and MPPF using liquid chromatography electrospray ionization tandem mass spectrometry in rat plasma and brain tissue
08 January 2013,
02:17:56
15 January 2013
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
A simple, selective, and sensitive liquid chromatography electrospray ionization tandem mass spectrometry (LC–ESI-MS/MS) method was validated for the determination of 4-fluoromethyl-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexane-1-carboxamide (MEFWAY) and 4-fluoro-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)benzamide (MPPF) in rat plasma and brain samples, respectively. Plasma and brain samples were extracted with a mixture of acetonitrile and methanol (1:1, v/v) and then separated on a C18 column (Gemini 3μm 110Å, 50×2.00mm ID, Phenomenex, USA). Quantitation was performed using LC–ESI-MS/MS in multiple-reaction monitoring (MRM) mode with positive ion electrospray ionization (ESI). The limit of quantification (LOQ) of 5ng/mL and 1ng/mL were obtained in 50μL brain homogenate and plasma, respectively. The analytical linear ranges of this method were 1–4000ng/mL in plasma and 5–4000ng/mL in brain homogenate with a correlation coefficients (R 2) greater than 0.9993. The intra- and inter-day precision and accuracy values were within the assay validation guideline (lower than 13.0%). The analytes in plasma and brain samples were stable after three freeze–thaw cycles, long-term storage (one month at −80°C), and short-term (4h) storage at room temperature. The present method was successfully applied to plasma-brain pharmacokinetic studies to investigate brain penetration of a single dose of MEFWAY and MPPF in rats.
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
A simple, selective, and sensitive liquid chromatography electrospray ionization tandem mass spectrometry (LC–ESI-MS/MS) method was validated for the determination of 4-fluoromethyl-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexane-1-carboxamide (MEFWAY) and 4-fluoro-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)benzamide (MPPF) in rat plasma and brain samples, respectively. Plasma and brain samples were extracted with a mixture of acetonitrile and methanol (1:1, v/v) and then separated on a C18 column (Gemini 3μm 110Å, 50×2.00mm ID, Phenomenex, USA). Quantitation was performed using LC–ESI-MS/MS in multiple-reaction monitoring (MRM) mode with positive ion electrospray ionization (ESI). The limit of quantification (LOQ) of 5ng/mL and 1ng/mL were obtained in 50μL brain homogenate and plasma, respectively. The analytical linear ranges of this method were 1–4000ng/mL in plasma and 5–4000ng/mL in brain homogenate with a correlation coefficients (R 2) greater than 0.9993. The intra- and inter-day precision and accuracy values were within the assay validation guideline (lower than 13.0%). The analytes in plasma and brain samples were stable after three freeze–thaw cycles, long-term storage (one month at −80°C), and short-term (4h) storage at room temperature. The present method was successfully applied to plasma-brain pharmacokinetic studies to investigate brain penetration of a single dose of MEFWAY and MPPF in rats.
Highlights
► A simple, rapid, and sensitive LC–ESI-MS/MS method of MEFWAY and MPPF. ► Validation for the determination of MEFWAY and MPPF in rat plasma and brain. ► The sample preparation followed by one-step protein precipitation using acetonitrile and methanol. ► The assay variability limits set forth in the FDA guidelines. ► The present method can be applied to plasma-brain pharmacokinetic studies to investigate brain penetration in rats.Quantitative determination of capecitabine and its six metabolites in human plasma using liquid chromatography coupled to electrospray tandem mass spectrometry
08 January 2013,
02:17:56
15 January 2013
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
Capecitabine is the oral prodrug of the anticancer drug 5-fluorouracil (5-FU). The purpose of this study was to quantify capecitabine and its metabolites including 5′-deoxy-5-fluorocytidine (5′-dFCR), 5′-deoxy-5-fluorouridine (5′-dFUR), 5-FU, dihydro-5-fluorouracil (FUH2), α-fluoro-ureidopropionic acid (FUPA) and fluoro-β-alanine (FBAL) in human plasma using liquid chromatography coupled to electrospray tandem mass spectrometry. To this end two individual assays were developed: one for the simultaneous quantification of capecitabine, 5′-dFCR and 5′-dFUR using reversed phase chromatography and gradient elution, and one assay for 5-FU, FUH2, FUPA and FBAL using hydrophilic interaction chromatography and isocratic elution. Both assays were fully validated according to current FDA guidelines. Total run time for the capecitabine assay was 9.0min, and of the 5-FU assay 5.0min. Analyte extraction was performed by protein precipitation. Stable labeled isotopes for each of the analytes were used as internal standards. The linear ranges of the analytes were 50–6000ng/mL for the capecitabine assay and 50–5000ng/mL for the 5-FU assay. Validation results demonstrate that capecitabine and its metabolites can be rapidly, accurately, precisely and robustly quantified in human plasma with the presented methods. Both assays are currently in extensive use in support of pharmacokinetic studies in patients treated with capecitabine or 5-FU.
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
Capecitabine is the oral prodrug of the anticancer drug 5-fluorouracil (5-FU). The purpose of this study was to quantify capecitabine and its metabolites including 5′-deoxy-5-fluorocytidine (5′-dFCR), 5′-deoxy-5-fluorouridine (5′-dFUR), 5-FU, dihydro-5-fluorouracil (FUH2), α-fluoro-ureidopropionic acid (FUPA) and fluoro-β-alanine (FBAL) in human plasma using liquid chromatography coupled to electrospray tandem mass spectrometry. To this end two individual assays were developed: one for the simultaneous quantification of capecitabine, 5′-dFCR and 5′-dFUR using reversed phase chromatography and gradient elution, and one assay for 5-FU, FUH2, FUPA and FBAL using hydrophilic interaction chromatography and isocratic elution. Both assays were fully validated according to current FDA guidelines. Total run time for the capecitabine assay was 9.0min, and of the 5-FU assay 5.0min. Analyte extraction was performed by protein precipitation. Stable labeled isotopes for each of the analytes were used as internal standards. The linear ranges of the analytes were 50–6000ng/mL for the capecitabine assay and 50–5000ng/mL for the 5-FU assay. Validation results demonstrate that capecitabine and its metabolites can be rapidly, accurately, precisely and robustly quantified in human plasma with the presented methods. Both assays are currently in extensive use in support of pharmacokinetic studies in patients treated with capecitabine or 5-FU.
Highlights
► Simultaneous quantification of capecitabine and all its six metabolites in plasma. ► Assay fully validated according to current FDA guidelines. ► Rapid, robust, selective and sensitive method using HPLC–tandem mass spectrometry.A sensitive and selective quantification of catecholamine neurotransmitters in rat microdialysates by pre-column dansyl chloride derivatization using liquid chromatography–tandem mass spectrometry
08 January 2013,
02:17:56
15 January 2013
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
A rapid and sensitive liquid chromatography tandem mass spectrometry method for simultaneous quantification of catecholamine neurotransmitters in microdialysates was developed. The catecholamine neurotransmitters dopamine (DA) and norepinephrine (NE) were pre-column derivatized with dansyl chloride and analyzed. A gradient elution method was used to separate the analytes from the interferences on an Agilent Poroshell 120 EC-C18 outer porous micro particulate column. The method was robust and sensitive to determine with the lower limit of quantification value of 0.068pmol/mL and 0.059pmol/mL for DA and NE, respectively. It has acceptable precision and accuracy for concentrations over the standard curve range. The method was successfully applied for simultaneous quantitation of DA and NE in the prefrontal cortex (PFC) dialysates of rats obtained from a microdialysis study dosed with vehicle and atomoxetine through intra peritoneal (i.p.) route at a dose of 3mg/kg to monitor the change in extracellular concentrations. Thus, accomplishment of this method would facilitate the neurochemical monitoring for discovery of new chemical entities targeted for the treatment of attention deficit hyperactivity disorder (ADHD).
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
A rapid and sensitive liquid chromatography tandem mass spectrometry method for simultaneous quantification of catecholamine neurotransmitters in microdialysates was developed. The catecholamine neurotransmitters dopamine (DA) and norepinephrine (NE) were pre-column derivatized with dansyl chloride and analyzed. A gradient elution method was used to separate the analytes from the interferences on an Agilent Poroshell 120 EC-C18 outer porous micro particulate column. The method was robust and sensitive to determine with the lower limit of quantification value of 0.068pmol/mL and 0.059pmol/mL for DA and NE, respectively. It has acceptable precision and accuracy for concentrations over the standard curve range. The method was successfully applied for simultaneous quantitation of DA and NE in the prefrontal cortex (PFC) dialysates of rats obtained from a microdialysis study dosed with vehicle and atomoxetine through intra peritoneal (i.p.) route at a dose of 3mg/kg to monitor the change in extracellular concentrations. Thus, accomplishment of this method would facilitate the neurochemical monitoring for discovery of new chemical entities targeted for the treatment of attention deficit hyperactivity disorder (ADHD).
Highlights
► Dansyl chloride derivatization of dopamine and norepinephrine in rat microdialysates. ► Sensitive and selective method to determine the basal levels in rat prefrontal cortex. ► Good peak resolution and separation from the interferences using superficial porous micro particulate column. ► Selective method in the neurochemical monitoring for discovery of new chemical entities targeted for the treatment of ADHD. ► The method demonstrated can be applicable in other regions such as medial PFC, striatum and hippocampus.Keto acid profiling analysis as ethoxime/tert-butyldimethylsilyl derivatives by gas chromatography–mass spectrometry
08 January 2013,
02:17:56
15 January 2013
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
Organic acids, including keto acids, are key intermediates of central pathways in cellular metabolism. In this study, a comprehensive and reliable method was developed and optimized for the simultaneous measurement of 17 keto acids in various biological samples. The keto acids were converted to solvent extractable forms by ethoximation followed by tert-butyldimethylsilylation for direct analysis by gas chromatography–mass spectrometry in selected ion monitoring mode. The proposed method was precise (0.05–8.3, % RSD) and accurate (−10.5 to 5.3, % RE) with low limit of detection (0.01–0.5ng/mL) and good linearity (r >0.995) in the range of 0.01–5.0μg/mL. This was suitable for profiling analysis of targeted keto acids in human plasma, urine and rat brain tissue.
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
Organic acids, including keto acids, are key intermediates of central pathways in cellular metabolism. In this study, a comprehensive and reliable method was developed and optimized for the simultaneous measurement of 17 keto acids in various biological samples. The keto acids were converted to solvent extractable forms by ethoximation followed by tert-butyldimethylsilylation for direct analysis by gas chromatography–mass spectrometry in selected ion monitoring mode. The proposed method was precise (0.05–8.3, % RSD) and accurate (−10.5 to 5.3, % RE) with low limit of detection (0.01–0.5ng/mL) and good linearity (r >0.995) in the range of 0.01–5.0μg/mL. This was suitable for profiling analysis of targeted keto acids in human plasma, urine and rat brain tissue.
Highlights
► 17 keto acids as to ethoxime/tert-butyldimethylsilyl derivatives were analyzed by GC–MS. ► The optimal method showed good precision, accuracy and sensitivity. ► The method was suitable for simultaneous analysis of 17 keto acids in biological samples.Quantitative determination of diterpenoid alkaloid Fuziline by hydrophilic interaction liquid chromatography (HILIC)–electrospray ionization mass spectrometry and its application to pharmacokinetic study in rats
08 January 2013,
02:17:56
15 January 2013
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
A rapid, sensitive and specific hydrophilic interaction liquid chromatography coupled to electrospray ionization mass spectrometric (HILIC–MS) method for the quantification of Fuziline (15α-Hydroxyneoline) in rat plasma was developed and validated. After liquid–liquid extraction with ethyl acetate, Fuziline and Guanfu base A (internal standard) were separated with HILIC Chrom Matrix HP amide column (5μm, 10cm×3.0mm I.D.) with isocratic elution at a flow-rate of 0.2mL/min. The analytes were detected by using an electrospray positive ionization mass spectrometry in the selected ion monitoring (SIM) mode. A good linear relationship was obtained in the concentration ranging from 1 to 1000ng/mL (R 2 =0.999) with the lower limit of quantification (LLOQ) at 1ng/mL and limit of detection (LOD) at 0.5ng/mL. The average recoveries of Fuziline in plasma at the concentrations of 2, 50, 1000ng/mL ranged from 68.2 to 69.9%. Intra- and inter-batch relative standard deviations ranged from 1.5 to 3.3% and 2.6 to 8.3%, respectively. Fuziline was stable under different sample storage and processing conditions except three-cycle freeze–thaw treatment at 2ng/mL. This method was successfully applied to the pharmacokinetic studies in Sprague-Dawley rats. The absolute bioavailability of Fuziline after oral administration 4mg/kg Fuziline in rats was 21.1±7.0%, with clearance rate at 1745.6±818.1mL/kg/h, and half-life at about 6.3±2.6h.
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
A rapid, sensitive and specific hydrophilic interaction liquid chromatography coupled to electrospray ionization mass spectrometric (HILIC–MS) method for the quantification of Fuziline (15α-Hydroxyneoline) in rat plasma was developed and validated. After liquid–liquid extraction with ethyl acetate, Fuziline and Guanfu base A (internal standard) were separated with HILIC Chrom Matrix HP amide column (5μm, 10cm×3.0mm I.D.) with isocratic elution at a flow-rate of 0.2mL/min. The analytes were detected by using an electrospray positive ionization mass spectrometry in the selected ion monitoring (SIM) mode. A good linear relationship was obtained in the concentration ranging from 1 to 1000ng/mL (R 2 =0.999) with the lower limit of quantification (LLOQ) at 1ng/mL and limit of detection (LOD) at 0.5ng/mL. The average recoveries of Fuziline in plasma at the concentrations of 2, 50, 1000ng/mL ranged from 68.2 to 69.9%. Intra- and inter-batch relative standard deviations ranged from 1.5 to 3.3% and 2.6 to 8.3%, respectively. Fuziline was stable under different sample storage and processing conditions except three-cycle freeze–thaw treatment at 2ng/mL. This method was successfully applied to the pharmacokinetic studies in Sprague-Dawley rats. The absolute bioavailability of Fuziline after oral administration 4mg/kg Fuziline in rats was 21.1±7.0%, with clearance rate at 1745.6±818.1mL/kg/h, and half-life at about 6.3±2.6h.
Highlights
► A HILIC–ESI-MS was developed for the detection of Fuziline in rat plasma. ► The pharmacokinetic of fuziline in rats was studied for the first time. ► The absolute bioavailability of Fuziline after i.g. in rats (4mg/kg) was 21.1±7.0%.Evaluation of molecularly imprinted anion-functionalized poly(ionic liquid)s by multi-phase dispersive extraction of flavonoids from plant
08 January 2013,
02:17:56
15 January 2013
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
Molecularly imprinted anion-functionalized poly(ionic liquid)s (MAPILs) were prepared by radical polymerization for the multi-phase dispersive extraction (MPDE) of flavonoids from plants. Poly(ionic liquid)s were functionalized with different anions via anion metathesis to enhance their separation efficiency, called anion-functionalized poly(ionic liquid)s (APILs). A molecularly imprinting technique was introduced to produce specific recognition sites by forming complexes between the template molecules and anion-functionalized ionic liquid monomers to reduce the interactions with the interference substances and increase the selectivity. Multi-phase dispersive extraction (MPDE) was applied for separation instead of the traditional solid phase extraction method. The target compounds were first extracted by three-phase (sample–solvent–sorbent) dispersive extraction and cleaned up after removing the sample matrix. This method significantly decrease in the interference and analysis cost. A suitable sorbent for MPDE could be identified based on the adsorption behaviors of flavonoids on different MAPILs. The mean recovery yields of quercitrin, myricetin, and amentoflavone from Chamaecyparis obtusa under the optimized conditions were 88.07, 93.59, and 95.13%. This is a promising method for the extraction, separation and determination of flavonoids or other polyphenolic compounds from natural and other sources.
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
Molecularly imprinted anion-functionalized poly(ionic liquid)s (MAPILs) were prepared by radical polymerization for the multi-phase dispersive extraction (MPDE) of flavonoids from plants. Poly(ionic liquid)s were functionalized with different anions via anion metathesis to enhance their separation efficiency, called anion-functionalized poly(ionic liquid)s (APILs). A molecularly imprinting technique was introduced to produce specific recognition sites by forming complexes between the template molecules and anion-functionalized ionic liquid monomers to reduce the interactions with the interference substances and increase the selectivity. Multi-phase dispersive extraction (MPDE) was applied for separation instead of the traditional solid phase extraction method. The target compounds were first extracted by three-phase (sample–solvent–sorbent) dispersive extraction and cleaned up after removing the sample matrix. This method significantly decrease in the interference and analysis cost. A suitable sorbent for MPDE could be identified based on the adsorption behaviors of flavonoids on different MAPILs. The mean recovery yields of quercitrin, myricetin, and amentoflavone from Chamaecyparis obtusa under the optimized conditions were 88.07, 93.59, and 95.13%. This is a promising method for the extraction, separation and determination of flavonoids or other polyphenolic compounds from natural and other sources.
Highlights
► Poly(ionic liquid)s with different functional anions were developed. ► The anion-functionalized poly(ionic liquid)s were achieved anion metathesis. ► The anion-functionalized polymers were upgraded with molecularly imprinting. ► Multi-phase dispersive extraction was developed for the extraction and clean-up.Identification of characteristic flavour precursors from enzymatic hydrolysis-mild thermal oxidation tallow by descriptive sensory analysis and gas chromatography–olfactometry and partial least squares regression
08 January 2013,
02:17:56
15 January 2013
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
The “enzymatic hydrolysis-mild thermal oxidation” method was employed to obtain oxidized tallow. Nine beeflike flavours (BFs) were prepared through Maillard reaction with oxidized tallow and other ingredients. Volatile compounds of oxidized tallow and beeflike flavours were analysed by SPME/GC–MS. Six sensory attributes (meaty, beefy, tallowy, simulate, burnt and off-flavour) were selected to assess BFs. Thirty four odour-active compounds were identified to represent beef odour through GC–O analysis based on detection frequency method. GC–MS profiles of oxidized tallow were correlated with GC–O responses and sensory attributes of BFs using partial least squares regression modelling (PLSR). Twenty nine compounds were considered as the potential precursors of oxidized tallow. Among them, tetradecanoic acid, d-limonene, 1,7-heptandiol, 2-butyltetrahydrofuran, (Z)-4-undecenal, (Z)-4-decenal, (E)-4-nonenal and 5-pentyl-2(3H)-furanone were unique products generated from enzymatic hydrolysis-mild thermal oxidation of tallow, while hexanal, heptanal, octanal, nonanal, decanal, pentanal, acetic acid, butanoic acid, hexanoic acid, 1-heptanol, 1-octanol, 3-methylbutanal, 2-pentylfuran, γ-nonalactone, 2-undecenal, (E,E)-2,4-decadienal, (E,E)-2,4-nonadienal, (E)-2-nonenal, (E)-2-octenal, (E)-2-decenal and (Z)-2-heptenal were common products generated from thermal oxidation of tallow.
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
The “enzymatic hydrolysis-mild thermal oxidation” method was employed to obtain oxidized tallow. Nine beeflike flavours (BFs) were prepared through Maillard reaction with oxidized tallow and other ingredients. Volatile compounds of oxidized tallow and beeflike flavours were analysed by SPME/GC–MS. Six sensory attributes (meaty, beefy, tallowy, simulate, burnt and off-flavour) were selected to assess BFs. Thirty four odour-active compounds were identified to represent beef odour through GC–O analysis based on detection frequency method. GC–MS profiles of oxidized tallow were correlated with GC–O responses and sensory attributes of BFs using partial least squares regression modelling (PLSR). Twenty nine compounds were considered as the potential precursors of oxidized tallow. Among them, tetradecanoic acid, d-limonene, 1,7-heptandiol, 2-butyltetrahydrofuran, (Z)-4-undecenal, (Z)-4-decenal, (E)-4-nonenal and 5-pentyl-2(3H)-furanone were unique products generated from enzymatic hydrolysis-mild thermal oxidation of tallow, while hexanal, heptanal, octanal, nonanal, decanal, pentanal, acetic acid, butanoic acid, hexanoic acid, 1-heptanol, 1-octanol, 3-methylbutanal, 2-pentylfuran, γ-nonalactone, 2-undecenal, (E,E)-2,4-decadienal, (E,E)-2,4-nonadienal, (E)-2-nonenal, (E)-2-octenal, (E)-2-decenal and (Z)-2-heptenal were common products generated from thermal oxidation of tallow.
Highlights
► The “enzymatic hydrolysis-mild thermal oxidation” method has been developed. ► The new method makes beeflike flavours more similar to natural beef flavour. ► The precursors of oxidized tallow are identified using PLSR.Analytical method for urinary metabolites of the fluorine-containing pyrethroids metofluthrin, profluthrin and transfluthrin by gas chromatography/mass spectrometry
08 January 2013,
02:17:56
15 January 2013
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
An analytical method was developed for measurement of the major urinary metabolites in rats administered fluorine-containing pyrethroids (metofluthrin, profluthrin and transfluthrin) which are widely used recently as mosquito repellents or mothproof repellents. Eight metabolites, 2,3,5,6-tetrafluorobenzoic acid, 4-methyl-2,3,5,6-tetrafluorobenzoic acid, 2,2-dimethyl-3-(1-propenyl)-cyclopropanecarboxylic acid, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (carboxylic metabolites), 2,3,5,6-tetrafluorobenzyl alcohol, 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol, 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol and 4-hydroxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (alcoholic metabolites), were extracted from enzymatic hydrolyzed urine using toluene and then concentrated. After transformation to their tert-butyldimethylsilyl derivatives for carboxylic metabolites or their trimethylsilyl derivatives for alcoholic metabolites, analysis was conducted by gas chromatography/mass spectrometry in the electron impact ionization mode. The calibration curves for each metabolite were linear over the concentration range of 0–20μg/ml in urine, and the quantification limits were between 0.009 and 0.03μg/ml. The relative errors and the relative standard deviations on replicate assays were less than 6% and 5%, respectively, for all concentrations studied. The measurements were accurate and precise. The collected urine samples could be stored for up to 1 month at −20°C in a freezer. The proposed method was applied to the analysis of several urine samples collected from rats treated with these pyrethroids.
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
An analytical method was developed for measurement of the major urinary metabolites in rats administered fluorine-containing pyrethroids (metofluthrin, profluthrin and transfluthrin) which are widely used recently as mosquito repellents or mothproof repellents. Eight metabolites, 2,3,5,6-tetrafluorobenzoic acid, 4-methyl-2,3,5,6-tetrafluorobenzoic acid, 2,2-dimethyl-3-(1-propenyl)-cyclopropanecarboxylic acid, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (carboxylic metabolites), 2,3,5,6-tetrafluorobenzyl alcohol, 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol, 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol and 4-hydroxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (alcoholic metabolites), were extracted from enzymatic hydrolyzed urine using toluene and then concentrated. After transformation to their tert-butyldimethylsilyl derivatives for carboxylic metabolites or their trimethylsilyl derivatives for alcoholic metabolites, analysis was conducted by gas chromatography/mass spectrometry in the electron impact ionization mode. The calibration curves for each metabolite were linear over the concentration range of 0–20μg/ml in urine, and the quantification limits were between 0.009 and 0.03μg/ml. The relative errors and the relative standard deviations on replicate assays were less than 6% and 5%, respectively, for all concentrations studied. The measurements were accurate and precise. The collected urine samples could be stored for up to 1 month at −20°C in a freezer. The proposed method was applied to the analysis of several urine samples collected from rats treated with these pyrethroids.
Highlights
► We develop an analytical method of metabolites of fluorine-containing pyrethroids. ► They are used widely recently as mosquito repellents or moth-repellents in houses. ► The metabolites from hydrolyzed urine are analyzed by GC/MS(EI) after derivatization. ► They can be measured accurately and precisely. ► The collected urine samples can be stored for up to 1 month at −20°C in a freezer.Development and validation of an LC–MS/MS method for the determination of tolvaptan in human plasma and its application to a pharmacokinetic study
08 January 2013,
02:17:56
15 January 2013
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
Tolvaptan is a selective vasopressin V2-receptor antagonist mainly used for the treatment of hyponatremia. This study described the development and validation of an LC–MS/MS method for the determination of tolvaptan in human plasma. Sample preparation involved protein precipitation with acetonitrile containing 2-demethyl tolvaptan (internal standard, IS). Chromatographic separation was performed on a Zorbax XDB C18 column with an isocratic mobile phase consisting of water (containing 0.1% formic acid) and methanol (25:75, v/v). Determination of the analytes was achieved by tandem-mass spectrometry with positive electrospray ionization. The multiple reaction monitoring (MRM) transitions were performed at m/z 449.2→252.1 for tolvaptan and m/z 435.2→238.1 for IS. The assay was linear over the concentration range of 0.457–1000ng/mL, with a lower limit of quantification of 0.457ng/mL. The intra- and inter-day precisions at three concentration levels (0.914, 111 and 800ng/mL) were less than 15% and their accuracies were within the range of 97.7–107.8%. The mean recovery ranged from 99.2 to 104.6% and the matrix effect from 89.3 to 99.5%. Tolvaptan was stable under all tested conditions. This validated method was successfully applied to a pharmacokinetic study in healthy volunteers after oral administration of single-dose tolvaptan tablets.
Publication year: 2013
Source:Journal of Chromatography B, Volumes 913–914
Tolvaptan is a selective vasopressin V2-receptor antagonist mainly used for the treatment of hyponatremia. This study described the development and validation of an LC–MS/MS method for the determination of tolvaptan in human plasma. Sample preparation involved protein precipitation with acetonitrile containing 2-demethyl tolvaptan (internal standard, IS). Chromatographic separation was performed on a Zorbax XDB C18 column with an isocratic mobile phase consisting of water (containing 0.1% formic acid) and methanol (25:75, v/v). Determination of the analytes was achieved by tandem-mass spectrometry with positive electrospray ionization. The multiple reaction monitoring (MRM) transitions were performed at m/z 449.2→252.1 for tolvaptan and m/z 435.2→238.1 for IS. The assay was linear over the concentration range of 0.457–1000ng/mL, with a lower limit of quantification of 0.457ng/mL. The intra- and inter-day precisions at three concentration levels (0.914, 111 and 800ng/mL) were less than 15% and their accuracies were within the range of 97.7–107.8%. The mean recovery ranged from 99.2 to 104.6% and the matrix effect from 89.3 to 99.5%. Tolvaptan was stable under all tested conditions. This validated method was successfully applied to a pharmacokinetic study in healthy volunteers after oral administration of single-dose tolvaptan tablets.
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