Current Issue : January - March Volume : 2015 Issue Number : 1 Articles : 7 Articles
Olaparib (AZD2281) is an orally active PARP-1 inhibitor, primarily effective\nagainst cancers with BRCA1/2 mutations. It is currently in Phase III development and\nhas previously been investigated in numerous clinical trials, both as a single agent and in\ncombination with chemotherapy. Despite this widespread testing, there is only one published\nmethod that provides assay details and stability studies for olaparib alone. A more sensitive\nuHPLC-MS/MS method for the quantification of olaparib in human plasma was developed,\nincreasing the range of quantification at both ends (0.5ââ?¬â??50,000 ng/mL) compared to previously\npublished methods (10ââ?¬â??5,000 ng/mL). The wider range encompasses CMAX levels produced\nby typical olaparib doses and permits better pharmacokinetic modeling of olaparib\nelimination. This assay also utilizes a shorter analytical runtime, allowing for more rapid\nquantification and reduced use of reagents. A liquid-liquid extraction was followed by\nchromatographic separation on a Waters UPLCÃ?® BEH C18 column (2.1 Ã?â?? 50 mm, 1.7 ?m)\nand mass spectrometric detection. The mass transitions m/z 435.4281.1 and m/z\n443.2281.1 were used for olaparib and the internal standard [2H8]-olaparib, respectively.\nThe assay proved to be accurate (<9% deviation) and precise (CV < 11%). Stability studies showed that olaparib is stable at room temperature for 24 h. in whole blood, at 4 Ã?°C for\n24 h post-extraction, at 80 Ã?°C in plasma for at least 19 months, and through three\nfreeze-thaw cycles. This method proved to be robust for measuring olaparib levels in\nclinical samples from a Phase I trial....
This study presents the optimization of a simple HPLC-UV method for the determination of asenapine maleate in rat plasma. Ion pair separation followed by UV detection was performed on deproteinized rat plasma samples. The separation was carried out on a cosmosil C-18 column (250 mm × 4.6 mm, 5 µm) with UV detection at 232 nm. The mobile phase contained acetonitrile: potassium dihydrogen phosphate buffer pH 3.2 (60:40 v/v). The mobile phase was run isocratically. The flow rate of the mobile phase was maintained at 1 ml/min. The linearity of the calibration curve was obtained in the concentration range of 10 to 100 µg/ml for asenapine maleate and coefficient of correlation (R2) was found to be 0.997. The lowest limit of detection and quantification was 0.188 and 0.57 ng/ml respectively. No endogenous substances were found to interfere with the peaks of drug and plasma. The intra-day and inter-day coefficient of variations was less for all the selected concentrations. This method was time efficient and samples are easy to prepare with minimum dilution. So, it can be applied for monitoring asenapine maleate in rat plasma....
A reverse phase stability indicating HPLC method for simultaneous determination of two antispasmodic drugs in pharmaceutical\nparenteral dosage forms (injectable) and in serum has been developed and validated. Mobile phase ingredients consist of\nAcetonitrile : buffer : sulfuric acid 0.1M (50 : 50 : 0.3 v/v/v), at flow rate 1.0 mL/min using a Hibar ????Bondapak ODS C18 column\nmonitored at dual wavelength of 266nm and 205nm for phloroglucinol and trimethylphloroglucinol, respectively. The drugs\nwere subjected to stress conditions of hydrolysis (oxidation, base, acid, and thermal degradation). Oxidation degraded the\nmolecule drastically while there was not so much significant effect of other stress conditions. The calibration curve was linear\nwith a correlation coefficient of 0.9999 and 0.9992 for PG and TMP, respectively. The drug recoveries fall in the range of\n98.56% and 101.24% with 10 pg/mL and 33 pg/mL limit of detection and limit of quantification for both phloroglucinol and\ntrimethylphloroglucinol. The method was validated in accordance with ICH guidelines and was applied successfully to quantify\nthe amount of trimethylphloroglucinol and phloroglucinol in bulk, injectable form and physiological fluid. Forced degradation\nstudies proved the stability indicating abilities of the method....
The aim of this study was to develop and validate a high-performance liquid chromatographic-tandem mass spectrometric (LCMS/\nMS) method for analysis of the amiridine in human plasma. The analyte and internal standard (IS), zolpidem, were extracted\nfrom human plasma by solid phase extraction (SPE with SOLA cartridges) and separated on a Zorbax SB-C18 column using\nmethanol and 0.2% formic acid in water as mobile phase. Detection was performed using an electrospray ionization source and\nmass spectrometric positive multireaction monitoring mode (+MRM) at a voltage capillary of +2000V. The assay was linear over\nthe concentration range 0.5ââ?¬â??200 ng/mL with the lowest limit of quantification (LLOQ) of 0.5 ng/mL. The method also afforded\nsatisfactory results in terms of the sensitivity, specificity, precision (intra- and interday CV < 12%), accuracy, recovery, and the\nstability of the analyte under various conditions. The method can be successfully applied to pharmacokinetic studies....
Photocyanine is a novel anticancer drug. Its pharmacokinetic study in cancer patients is therefore very important for choosing\ndoses, and dosing intervals in clinical application. A rapid, selective and sensitive high-performance liquid chromatographytandem\nmass spectrometry (HPLC-MS/MS) method was developed and validated for the determination of photocyanine in patient\nserum. Sample preparation involved one-step protein precipitation by adding methanol and N,N-dimethyl formamide to 0.1mL\nserum. The detection was performed on a triple quadrupole tandem mass spectrometer operating in multiple reaction-monitoring\n(MRM) mode. Each sample was chromatographed within 7 min. Linear calibration curves were obtained for photocyanine at a\nconcentration range of 20ââ?¬â??2000 ng/mL (???? > 0.995), with the lower limit of quantification (LLOQ) being 20 ng/mL. The intrabatch\naccuracy ranged from 101.98% to 107.54%, and the interbatch accuracy varied from 100.52% to 105.62%. Stability tests showed\nthat photocyanine was stable throughout the analytical procedure. This study is the first to utilize the HPLC-MS/MS method for\nthe pharmacokinetic study of photocyanine in six cancer patients who had received a single dose of photocyanine (0.1mg/kg)\nadministered intravenously....
This study presented the optimization of a simple HPLC-UV method for the determination of repaglinide (RPG) in\nhuman plasma. Chromatographic separation followed by UV detection was performed on deproteinized human plasma samples.\nThe separation was carried out on a cosmosil C-18 column (250 mm Ã?â?? 4.6 mm, 5 ?m) with UV detection at 230 nm. The mobile\nphase contained acetonitrile: ammonium acetate buffer pH 4 (80 : 20 v/v). The mobile phase was run isocratically. The flow rate\nof the mobile phase was maintained at 1 ml/min. The linearity of the calibration curve was obtained in the concentration range\nof 10 to 100 ?g/ml for repaglinide and coefficient of correlation (r2) was found to be 0.999. The lowest limit of detection and\nquantification was 10 and 20 ng/ml respectively. No endogenous substances were found to interfere with the peaks of drug and\nplasma. The intra-day and inter-day coefficient of variations was less for all the selected concentrations. This method was time\nefficient and samples are easy to prepare with minimum dilution. So, it can be applied for monitoring repaglinide in human\nplasma....
A simple, robust LC-MS/MS assay for quantifying cefuroxime in human plasma was developed. Cefuroxime and tazobactam,\nas internal standard (IS), were extracted from human plasma by methanol to precipitate protein. Separation was achieved on a\nZorbax SB-Aq (4.6 Ã?â?? 250 mm, 5 ?m) column under isocratic conditions. The calibration curve was linear in the concentration\nrange of 0.0525ââ?¬â??21.0 ?g/mL (r = 0.9998). The accuracy was higher than 90.92%, while the intra- and interday precision were\nless than 6.26%. The extraction procedure provides recovery ranged from 89.44% to 92.32%, for both analyte and IS. Finally, the\nmethod was successfully applied to a bioequivalence study of a single 500mg dose of cefuroxime axetil in 22 healthy Chinese male\nsubjects under fasting condition. Bioequivalence was determined by calculating 90%Cls for the ratios of Cmax, AUC0??, andAUC0??\nvalues for the test and reference products, using logarithmic transformed data.The 90% Cls for the ratios of Cmax (91.4%?104.2%),\nAUC0?? (97.4%?110.9%), and AUC0?? (97.6%?111.1%) values were within the predetermined range. It was concluded that the two\nformulations (test for capsule, reference for tablet) analyzed were bioequivalent in terms of rate and extent of absorption and the\nmethod met the principle of quick and easy clinical analysis....
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