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Pharmacokinetic Application (pharmacokinetic + application)
Selected AbstractsA sensitive and specific liquid chromatography/tandem mass spectrometry method for determination of echinacoside and its pharmacokinetic application in ratsBIOMEDICAL CHROMATOGRAPHY, Issue 6 2009Hao Yang Abstract A rapid and sensitive method based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the determination of echinacoside in rat plasma was established and fully validated. A single step of liquid,liquid extraction with n -butanol was utilized. Chromatographic separation of the analyte and the internal standard (IS), chlorogenic acid, from the sample matrix was performed using a Capcell-MG C18 analytical column (100 2.0 mm × 5 µm), with a gradient of acetonitrile and water containing 0.1% acetic acid as the mobile phase. Detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization source operated in negative ion selected reaction monitoring mode. The method was linear in the concentration range 10,2500 ng/mL. The deviations of both intra- and inter-day precisions (RSD) were 7.1% and the assay accuracies were within 99.2,106.5%. Echinacoside proved to be stable during sample storage, preparation and analysis when an antioxidant solution was used. The method was successfully applied to a pharmacokinetic study in rats after an intragastric administration of echinacoside (100 mg/kg). With the lower limit of quantification at 10 ng/mL, this method proved to have sufficient selectivity, sensitivity and reproducibility for the pharmacokinetic study of echinacoside. Copyright © 2009 John Wiley & Sons, Ltd. [source] Quantitative determination of ,,, -dimethylacrylshikonin (DASK) in rat whole blood by liquid chromatography,tandem mass spectrometry with pre-column derivation and its pharmacokinetic applicationBIOMEDICAL CHROMATOGRAPHY, Issue 4 2009Huifang Tian Abstract A sensitive and selective liquid chromatography,tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of ,,, -dimethylacrylshikonin (DASK) in rat whole blood. DASK was pretreated using pre-column derivatization with 2-mercaptoethanol followed by liquid,liquid extraction with cyclohexane. Detection was performed on Thermo Finnigan TSQ Quantum triple quadrupole mass spectrometer by selected reaction monitoring mode via electrospray ionization source. The linear range for the determination of DASK spiked in rat whole blood (0.25 mL) was 3,3000 ng/mL. The accuracy was within 9%. Intra- and inter-day precisions were no more than 16.1 and 13.3%, respectively. The validated LC-MS/MS method was successfully applied to the preliminary pharmacokinetic study in rats. After DASK administration (60 mg/kg, p.o.) in rats, pharmacokinetic parameters were obtained, where the area under the drug concentration,time curve was 2393.7 ± 224.4 ng h/mL and the elimination half-life was 27.6 ± 5.3 h. Copyright © 2008 John Wiley & Sons, Ltd. [source] Validation of a simple HPLC method for assay of haplamine and its metabolites in plasma suitable for pharmacokinetic application in ratsBIOMEDICAL CHROMATOGRAPHY, Issue 2 2008Sompheary Ea Abstract A simple HPLC method with ultraviolet detection has been developed and validated for the simultaneous determination of haplamine and its metabolites (trans/cis -3,4-dihydroxyhaplamine) in rat. A liquid,liquid extraction was used to extract the compounds from rat plasma. The analysis was performed on a C18 Nucleosil Nautilus column. The mobile phase consisted of water (A) and a mixture of methanol and acetonitrile (85:15; v/v) (B) used in gradient mode (38,40% B for 10 min, 40,58% B for 49 min, 58,38% B for 1 min, and 38% for 5 min) pumped at 1 mL/min. The calibration curves showed good linearity with correlation coefficients greater than 0.999 for the analytes in the investigated concentration range. The lower limit of detection was 0.007, 0.008 and 0.009 µg/mL and the lower limit of quantification was 0.014, 0.017 and 0.018 µg/mL for haplamine, and trans/cis -3,4-dihydroxyhaplamine, respectively. The method was applied to a preliminary pharmacokinetic study in rats. This method proved to meet fully the standards required of experimental pharmacokinetic studies and should be used in further preclinical investigation. Copyright © 2007 John Wiley & Sons, Ltd. [source] Validation of a simple HPLC method for DRF-4848, a novel COX-2 inhibitor suitable for pharmacokinetic application in rats,BIOMEDICAL CHROMATOGRAPHY, Issue 12 2006Raja Reddy Kallem Abstract For pharmacokinetic and toxicokinetic purpose a simple HPLC-UV method has been developed and validated for the estimation of DRF-4848, a novel COX-2 inhibitor in rat plasma. A liquid,liquid extraction was used to extract DRF-4848 and internal standard (IS, DRF-4367) from rat plasma. The analysis was performed on a C18 column with UV detection at 285 nm. The isocratic mobile phase, 0.01 m potassium dihydrogen ortho phosphate (pH 3.2) and acetonitrile (50:50, v/v) was run at a flow rate of 1 mL/min. The retention times of DRF-4848 and IS were 6.8 and 11.2 min, respectively. Absolute recovery for analyte and IS was >80% from rat plasma. A linear response was observed over a concentration range 0.1,20 mg/mL. The lower limit of quantification (LLOQ) of DRF-4848 was 0.1 mg/mL. The inter- and intra-day precisions in the measurement of quality control (QC) samples, 0.1, 0.3, 8.0 and 15.0 mg/mL, were in the range 1.74,8.70% relative standard deviation (RSD) and 0.75,8.43% RSD, respectively. Accuracy in the measurement of QC samples was in the range 93.29,116.51% of the nominal values. Analyte and IS were stable in the battery of stability studies viz., benchtop, autosampler, long-term and freeze/thaw cycles. Copyright © 2006 John Wiley & Sons, Ltd. [source] Atmospheric pressure desorption/ionization on silicon ion trap mass spectrometry applied to the quantitation of midazolam in rat plasma and determination of midazolam 1,-hydroxylation kinetics in human liver microsomesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 24 2006Rick C. Steenwyk The application of atmospheric pressure desorption/ionization on silicon (AP-DIOS) coupled with ion trap mass spectrometry (ITMS) was investigated for the quantification of midazolam in rat plasma, and determination of midazolam 1,-hydroxylation kinetics in pooled human liver microsomes. Results indicate good sensitivity with absolute detection limits for midazolam in rat plasma of approximately 300 femtograms. A linear dynamic range from approximately 10,5000,ng/mL was obtained in rat plasma with analysis times of 1,min per sample. Kinetic constants for midazolam 1,-hydroxylation in human liver microsomes yielded an apparent Km of 10.0,µM and Vmax of 6.4,nmol/min/mg. Studies investigating the inhibition of 1,-hydroxymidazolam formation by the cytochrome P450 3A4 model inhibitor ketoconazole yielded an IC50 of 0.03,µM. Quantitative precision for replicate analysis of rat plasma and human liver microsomal samples was variable with relative standard deviation (RSD) values ranging from a low of approximately 3% to over 50%, with the highest variability observed in data from human liver microsomal incubations. While preliminary studies investigating the application of AP-DIOS-ITMS suggested feasibility of this technique to typical pharmacokinetic applications, further work is required to understand the underlying causes for the high variability observed in these investigations. Copyright © 2006 John Wiley & Sons, Ltd. [source] | ||||||||||