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Dog Plasma (dog + plasma)
Selected AbstractsQuantitative analysis of the P-glycoprotein inhibitor Elacridar (GF120918) in human and dog plasma using liquid chromatography with tandem mass spectrometric detectionJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 10 2004Ellen Stokvis Abstract A liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method for the determination of the P-glycoprotein and breast cancer resistance protein inhibitor Elacridar in human and dog plasma is described. The internal standard was stable isotopically labelled Elacridar. Sample pretreatment involved liquid,liquid extraction with tert -butyl methyl ether. Analysis of Elacridar and internal standard was performed by reversed-phase LC on a basic stable minibore analytical column with an eluent consisting of acetonitrile and aqueous ammonia. An API-2000 triple-quadrupole mass spectrometer with an electrospray ion source was used in the positive-ion multiple reaction monitoring mode. The run time per sample was only 6 min. The method is sensitive and specific, with a dynamic range from 1 to 500 ng ml,1 from 100 µl of human or dog plasma. The accuracy of the method was within 15% bias and the precision was lower than 15% for all tested concentration levels and in both matrices. The method is simple and the liquid,liquid extraction produces clean samples. This method was successfully applied to support the pharmacokinetics of a clinical trial in which orally applied Elacridar was used as a bioavailability enhancer. Copyright © 2004 John Wiley & Sons, Ltd. [source] Development of a liquid chromatography/tandem mass spectrometry assay for the quantification of PM02734, a novel antineoplastic agent, in dog plasmaRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2006Jianming Yin A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay was developed and validated to quantify a novel antineoplastic agent, PM02734, in dog plasma. The method was validated to demonstrate the specificity, limit of quantification (LOQ), accuracy, and precision of measurements. The calibration range for PM02734 was established using PM02734 standards from 0.05 to 100,ng/mL in blank plasma. The dominating ions were doubly charged molecular ions [M+2H]2+ at m/z 740.0 instead of singly charged ones at m/z 1478.4. The selected reaction monitoring (SRM), based on the m/z 740.0,,,212.2 transition, was specific for PM02734, and that based on the m/z 743.8,,,212.2 transition was specific for deuterated PM02734 (the internal standard, IS); no endogenous materials interfered with the analysis of PM02734 and IS from blank plasma. The assay was linear over the concentration range 0.05,100,ng/mL. In terms of sensitivity of assay 0.05,ng/mL is a very low LLOQ, especially considering PM02734 is a peptide. The correlation coefficients for the calibration curves ranged from 0.9990 to 0.9999. The mean intraday and interday accuracies for all calibration standards (n,=,9) ranged from 93 to 111% (,11% bias) in dog plasma, and the mean interday precision for all calibration standards was less than 6.4%. The mean intra- and interday assay accuracy for all quality control replicates in dog plasma (n,=,9), determined at each QC level throughout the validated runs, ranged from 85,111% (,15% bias) and from 99,109% (,9% bias), respectively. The mean intra- and interday assay precision was less than 12.1 and 13.3% for all QC levels, respectively. The assay has been used to support preclinical pharmacokinetic (PK) and toxicokinetic studies. The results showed that preclinical samples could be monitored for PM02734 up to 168,h after dosing, which allowed us to identify multiple elimination phases and accurately estimate PK information. Copyright © 2006 John Wiley & Sons, Ltd. [source] Pharmacokinetic measurements of IDN 5390 using electrospray ionization tandem mass spectrometry: structure characterization and quantification in dog plasmaRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 24 2005Liguo Song In this report, electrospray ionization tandem mass spectrometry (ESI-MS/MS) for a pharmacokinetic study of IDN 5390, a novel C- seco taxane derivative, which is under preclinical evaluation, has been investigated. Our results showed that IDN 5390 and other taxanes including paclitaxel and IDN 5109 could ionize well in not only positive-, but also in negative-ion mode. Under collision-induced dissociation (CID) conditions, these compounds could fragment into similar M- (molecular), T- (taxane ring) and S- (side chain) series ions. In positive-ion ESI, the formation of both T- and S-series ions involved the breaking of the C-13 ester bond. In negative-ion ESI, however, while the formation mechanism of S-series ions remained the same, the breaking of the C-1, carboxylic ester bond resulted in T-series ions. At optimum collision energy (CE) values, M-, T- and S-series ions of IDN 5390 in both positive- and negative-ion ESI-MS/MS spectra had good intensity. This phenomenon makes both positive- and negative-ion ESI-MS/MS good methods for IDN 5390 metabolite structural characterization, i.e. to reveal the location of modification groups in IDN 5390 metabolites versus IDN 5390 either on the side chain or the taxane ring. A liquid chromatography (LC)/ESI-MS/MS method using the multiple-reaction monitoring (MRM) technique was thereafter developed to quantify IDN 5390 in dog plasma using paclitaxel as internal standard. The method was validated using a concentration range between 5 and 1000,ng/mL and had a limit of detection of 1,ng/mL. The inter-day %CV (%coefficient of variation) of the calibration standards ranged between 4.36 and 9.64%, the intra-day %CV of the calibration standards between 0.61 and 13.44%, and the mean % accuracy of the quality control samples at the low, middle and high end of the concentration curves were 12.5, 6.8 and 9.6%, respectively. Copyright © 2005 John Wiley & Sons, Ltd. [source] Determination and toxicokinetics comparison of ketamine and S(+)-ketamine in dog plasma by HPLC-MS methodBIOMEDICAL CHROMATOGRAPHY, Issue 3 2010Yu-xin Sheng Abstract ;A simple and reproducible method was developed for the quantification of ketamine and S(+)-ketamine in dog plasma using a high-performance liquid chromatography system coupled to a positive ion electrospray mass spectrometric analysis. Solid-phase extraction was used for extracting analytes from dog plasma samples. The analytes were separated on a Zorbax SB C18 column (100 × 2.1 mm, 3.5 ,m) with acetonitrile,formate buffer (10 mM ammonium formate and 0.3% formic acid) (17 : 83, v/v) as mobile phase at a flow-rate of 0.2 mL/min. Detection was operated under selected ion monitoring mode. [M + H]+ at m/z 238 for ketamine and S(+)-ketamine and [M + H]+ at m/z 180 for phenacetin (internal standard) were selected as detecting ions, respectively. The method was linear in the concentration range 51.6,2580 ng/mL. The intra- and inter-day precisions (RSD %) were within 11.3% and the assay accuracies ranged from 80.0 to 101.4%. Their average recoveries were greater than 91.1% at all test concentrations. The analytes were proved to be stable during all sample storage, preparation and analysis procedures. The method was successfully applied to the toxicokinetics study and comparison of ketamine and S (+)-ketamine following intravenous administration to dogs. Copyright © 2009 John Wiley & Sons, Ltd. [source] A simple and rapid high-performance liquid chromatography method for determination of alendronate sodium in beagle dog plasma with application to preclinical pharmacokinetic studyBIOMEDICAL CHROMATOGRAPHY, Issue 2 2010Jian Meng Abstract A simple and rapid high performance liquid chromatographic (HPLC) method for quantifying alendronate in beagle dog plasma was developed, validated and applied to a pharmacokinetic study. The sample preparation involved coprecipitation with CaCl2 and derivatization with o -phthalaldehyde. Chromatographic separation was achieved on a DiamonsilÔ C18 (250 × 4.6,mm, 5,µm) using acetonitrile,0.4% EDTA-Na2 (16:84, v/v) containing 0.034% of NaOH as mobile phase. The fluorimetric detector was operated at 339,nm (excitation) and 447 nm (emission). The linearity over the concentration range of 5.00,600,ng/mL for alendronate was obtained and the lower limit of quantification was 5.00,ng/mL. For each level of quality control samples, inter-day and intra-day precisions were less than 8.52 and 7.42% and accuracies were less than 9.07%. The assay was applied to the analysis of samples from a pharmacokinetic study. Following the oral administration of 70,mg alendronate sodium to beagle dogs, the maximum plasma concentration (Cmax) and elimination half-life were 152,±,27.3 and 1.75,± 0.267,h, respectively. The method was demonstrated to be highly feasible and reproducible for pharmacokinetic studies. Copyright © 2009 John Wiley & Sons, Ltd. [source] LC-MS/MS determination of 2-(4-((2-(2S,5R)-2-Cyano-5-ethynyl-1-pyrrolidinyl)-2-oxoethylamino)-4-methyl-1-piperidinyl)-4-pyridinecarboxylic acid (ABT-279) in dog plasma with high-throughput protein precipitation sample preparationBIOMEDICAL CHROMATOGRAPHY, Issue 11 2007Joseph Kim Abstract As an effective DPP-IV inhibitor, 2-(4-((2-(2S,5R)-2-Cyano-5-ethynyl-1-pyrrolidinyl)-2-oxoethylamino)-4-methyl-1-piperidinyl)-4-pyridinecarboxylic acid (ABT-279), is an investigational drug candidate under development at Abbott Laboratories for potential treatment of type 2 diabetes. In order to support the development of ABT-279, multiple analytical methods for an accurate, precise and selective concentration determination of ABT-279 in different matrices were developed and validated in accordance with the US Food and Drug Administration Guidance on Bioanalytical Method Validation. The analytical method for ABT-279 in dog plasma was validated in parallel to other validations for ABT-279 determination in different matrices. In order to shorten the sample preparation time and increase method precision, an automated multi-channel liquid handler was used to perform high-throughput protein precipitation and all other liquid transfers. The separation was performed through a Waters YMC ODS-AQ column (2.0 × 150 mm, 5 µm, 120 Å) with a mobile phase of 20 mm ammonium acetate in 20% acetonitrile at a flow rate of 0.3 mL/min. Data collection started at 2.2 min and continued for 2.0 min. The validated linear dynamic range in dog plasma was between 3.05 and 2033.64 ng/mL using a 50 µL sample volume. The achieved r2 coefficient of determination from three consecutive runs was between 0.998625 and 0.999085. The mean bias was between ,4.1 and 4.3% for all calibration standards including lower limit of quantitation. The mean bias was between ,8.0 and 0.4% for the quality control samples. The precision, expressed as a coefficient of variation (CV), was ,4.1% for all levels of quality control samples. The validation results demonstrated that the high-throughput method was accurate, precise and selective for the determination of ABT-279 in dog plasma. The validated method was also employed to support two toxicology studies. The passing rate was 100% for all 49 runs from one validation study and two toxicology studies. Copyright © 2007 John Wiley & Sons, Ltd. [source] Simultaneous determination and pharmacokinetic study of oxymatrine and matrine in beagle dog plasma after oral administration of Kushen formula granule, oxymatrine and matrine by LC-MS/MSBIOMEDICAL CHROMATOGRAPHY, Issue 8 2007Yiqi Wang Abstract A rapid, specific and sensitive LC-MS/MS method was developed for the determination of oxymatrine (OMT) and matrine (MT) in beagle dog plasma. The method was applied to study the pharmacokinetics of OMT and MT after oral administration of OMT, MT and Kushen formula granule (KFG) containing equivalent amounts of OMT and MT in a three-period crossover design. The analysis was carried out on an Acquity UPLCÔ BEH C18 column by linear gradient elution with 0.01% acetic acid,water,methanol as mobile phase. Detection was by positive ion electrospray ionization (ESI) mass spectrometry with multiple-reaction monitoring (MRM). Linear calibration curves were both obtained over the concentration range 15,2000 ng/mL, with a limit of quantification of 15 ng/mL. The matrix effect was minimized. The intra- and inter-day precisions (RSDs) were less than 12.4 and 14.7%, respectively, and the accuracy (RE) was from ,2.1 to 2.7%. The validated method was used to determine the concentration,time profiles of OMT and MT. The results indicated that the absorption of OMT and MT after oral administration of KFG was significantly greater than that after oral administration of pure components. Copyright © 2007 John Wiley & Sons, Ltd. [source] Liquid chromatographic/mass spectrometric assay of rabprazole in dog plasma for a pharmacokinetic studyBIOMEDICAL CHROMATOGRAPHY, Issue 11 2006Shao Feng Abstract In order to evaluate the pharmacokinetic (PK) profile of rabeprazole (RA) sterile powder for injection, a rapid, sensitive and specific assay for quantitative determination of RA in dog plasma was developed and validated. After a liquid,liquid extraction procedure, samples were analyzed by liquid chromatography,electrospray ionization mass spectrometry (LC-ESI-MS) using omepazole as the internal standard (IS). The analyte and IS was chromatographed on a ZORBAX Extend-C18 analytical column (50 × 2 mm i.d, 5 µm, Agilent Technologies, USA). The assay was linear in the range 1,2000 ng/mL. The lower limit of quantification of RA was 1 ng/mL. The recovery of RA was greater than 70%. The within- and between-batch accuracy was 102.7,107.4% and 103.5,105.7%, respectively. The plasma samples for the PK study were collected at defined time points during and after an intravenous injection (1 mg/kg) to beagle dogs and analyzed by LC-ESI-MS method. The PK parameters, such as half-life, volume of distribution, total clearance and elimination rate constant, were determined. The PK profile of RA gave insights into the application in the clinics. Copyright © 2006 John Wiley & Sons, Ltd. [source] Determination of picroside II in dog plasma by HPLC and its application in a pharmacokinetics studyBIOMEDICAL CHROMATOGRAPHY, Issue 4 2005Fu-Chuan Yang Abstract A sensitive and simple high-performance liquid chromatography method with UV detection was developed and validated for determining picroside II in dog plasma. Paeoni,orin was employed as internal standard and the sample pre-treatment procedure consists of deproteinization by addition of acetonitrile. Chromatographic separations were performed on a Shimadzu VP-ODS column (250 × 4.6 mm i.d., 5 µm). The mobile phase consisted of acetonitrile,0.1% acetic acid aqueous (v/v), 23:77, v/v, at a rate of 1 mL/min. Detection was carried out at a wavelength of 266 nm. Calibration standards ranged from 0.25 to 500 µg/mL in dog plasma and the mean correlation coef,cient of 0.9981 was found for the linear calibration curves (n = 6). The limit of quanti,cation (LOQ) was 0.25 µg/mL. Intra- and inter-assay RSD ranged from 0.70 to 7.5%. Accuracy (%bias) ranged from ,6.3 to 6.0%. This method was applied to the pharmacokinetic study of picroside II in dogs. The study demonstrated the plasma picroside II concentration,time curves were ,tted to the two-compartment open model and showed linear pharmacokinetics. Copyright © 2005 John Wiley & Sons, Ltd. [source] High performance liquid chromatographic,mass spectrometric assay for the quantitation of BMS-204352 in dog K3EDTA plasmaBIOMEDICAL CHROMATOGRAPHY, Issue 3 2002Ming Yao A high performance liquid chromatographic-mass spectrometric (LC/MS) assay was developed and validated for the determination of BMS-204352 in dog K3EDTA plasma. A 0.5,mL aliquot of control plasma was spiked with BMS-204352 and internal standard (IS) and buffered with 1,mL of 5,mM ammonium acetate. The mixture was then extracted with 3,mL of toluene. After separation and evaporation of the organic phase to dryness using nitrogen at 40°C, the residue was reconstituted in the mobile phase and 25,µL of the sample were injected onto a Hypersil C18 column (2,×,50,mm; 3,µm) at a flow rate of 0.5,mL/min. The mobile phase was consisted of two solvent mixtures (A and B). Solvent A was composed of 5,mM ammonium acetate and 0.1% triethylamine in 75:25 v/v water:methanol, pH adjusted to 5.5 with glacial acetic acid, and solvent B was 5,mM ammonium acetate in methanol. A linear gradient system was used to elute the analytes. The mass spectrometer was programmed to admit the de-protonated molecules at m/z 352.7 (IS) and m/z 357.9 (BMS-204352). Standard curves of BMS-204352 were linear (r2,,,0.998) over the concentration range of 0.5,1000,ng/mL. The mean predicted quality control (QC) concentrations deviated less than 5.1% from the corresponding nominal values (ie 4, 80, 400 and 2000,ng/mL); the within- and between-assay precision of the assay were within 5.5% relative standard deviation. Stability of BMS-204352 was confirmed after at least three freeze/thaw cycles and BMS-204532 was stable in dog plasma when stored frozen at or below ,20°C for at least 16 weeks in spiked QC samples and for at least 4 1/2 weeks for in vivo study samples. BMS-204352 and IS were stable in the injection solvent at room temperature for at least 24,h. The assay was applied to delineate the pharmacokinetic disposition of BMS-204352 in dogs following a single intravenous dose administration. In conclusion, the assay is accurate, precise, specific, sensitive and reproducible for the pharmacokinetic analysis of BMS-204532 in dog plasma. Copyright © 2002 John Wiley & Sons, Ltd. [source] Enantioselective LC/MS method for the determination of an antimalarial agent Fenozan B07 in dog plasmaCHIRALITY, Issue 5 2006Ciriaco Maraschiello Abstract A chiral liquid chromatography/mass spectrometry (LC/MS) bioanalytical procedure has been developed for the analysis of the antimalaric agent Fenozan B07 in dog plasma. Normal-phase chromatography involving a phenylcarbamate derivative of cellulose coated on silica gel as the chiral stationary phase was used to resolve (,)-(S,S)-B07 from (+)-(R,R)-B07. The enantiomers were detected by a mass spectrometer equipped with an atmospheric pressure chemical ionization (APCI) interface operated in the negative ion mode. A mass spectrum, characterized by a base peak of m/z 285, was obtained for each enantiomer. The m/z 285 ion was very specific for the analysis of both enantiomers in the plasma. The selected ion monitoring analysis of the plasma samples was therefore performed at m/z 285 for quantitative purposes. The enantiomers were extracted from the plasma in a basic medium and purified by solid-phase extraction using a hydrophilic,lipophilic balanced sorbent. A lower limit of quantification of 2 ng/mL in plasma was achieved for both enantiomers. The quantitative procedure reported in this study was highly specific and sensitive, and was validated according to the FDA guidance on bioanalytical method validation. Chirality, 2006. © 2006 Wiley-Liss, Inc. [source] | ||||||||||