Sensitive capillary gas chromatographic-mass spectrometric-selected-ion monitoring method for the determination of diclofenac concentrations in human plasma (original) (raw)
Related papers
Journal of chromatography, 1993
An assay using reversed-phase high-performance liquid chromatography with ultraviolet detection, at 278 nm, was developed to measure diclofenac in human plasma and urine at concentrations suitable for biopharmaceutical studies. Indomethacin was used as internal standard and separation was performed at 40 degrees C on a C18 Spherisorb column with acetonitrile-0.1 M sodium acetate (35:65, v/v) (pH 6.3) as mobile phase. The sample preparation is simple and rapid (extractionless), and the total run time is less than 5 min. The retention time is 2.8 min for diclofenac and 3.6 min for indomethacin. The detection limit is 0.2 microgram/ml using a 20-microliters loop.
Journal of Chromatography B: Biomedical Sciences and Applications, 2001
A novel high-performance liquid chromatographic (HPLC) method for the quantification of diclofenac in human plasma was set up. Samples, added with ibuprofen (used as internal standard) were purified by solid-phase extraction using Abselut Nexus cartridges (Varian) not requiring pre-conditioning. Drugs of interest were eluted directly into the autosampler vials and injected. The recovery of diclofenac was 92%, the analysis lasted
Turkish Journal of Pharmaceutical Sciences, 2016
A simple, rapid and reliable high performance liquid chromatography method (HPLC) with ultraviolet detection (UV) was developed and validated according to ICH guidelines, for quantitative analysis and therapeutic drug monitoring of diclofenac sodium (DS) in human plasma. Plasma samples (0.7 mL) were acid hydrolysis by 100 µL, 1 M hydrochloric acid. Analytes were concentrated from plasma by liquid-liquid extraction with 2 mL ethyl acetate by repeated twice, which allows to obtain good extraction yields (98.75%-99.32%). The separation was achieved by employing C18 analytical column (3.5 µm particle size, 150 mmx3.9 mm I.D.) under isocratic conditions using acetonitrile and NaH 2 PO 4 mixture (42.5:57.5, v/v) as mobile phase (pH: 3.16) flow rate of 1.5 mL/min. Naproxen (3 µg/mL) was used as an internal standard (IS). The DS and IS were detected at 281 nm and eluted at 2.6 and 6.2 min, respectively. Total run time was 7 min. Method showed linearity with very good determination coefficients (r 2 =0.999), over the concentration range of 50-1600 ng/mL. Limits of detection (LOD) and quantification (LOQ) were 8.95 ng/mL and 27.12 ng/mL, respectively. Intra-day precision and accuracy were between 0.93-5.27; 1.74-9.81, respectively. Inter-day precision and accuracy were between 2.71-6.64; 2.03-9.16, respectively. This method was successfully applied for determination of DS plasma concentrations during a pharmacokinetic study in healthy volunteers (n=12) after an oral administration of Voltaren ® 75 mg/tablet and remarkable variations in DS levels were observed. In our study, on the contrary to equivalent doses of DS, the observed significant differences in plasma levels of DS, on 2 nd , 4 th and 6 th hours, can be explained by pharmacokinetic differences, that arise from mainly polymorphisms of CYP2C9 and CYP3A4, which are major enzymes responsible for DS metabolism.
High-Throughput Ultra-Performance LC-MS-MS Method for Analysis of Diclofenac Sodium in Rabbit Plasma
Journal of Chromatographic Science, 2014
A new UPLC-MS-MS method was developed and validated for quantification of diclofenac sodium in rabbit plasma. Acetonitrile-based protein precipitation method was used to extract the drug from plasma samples. Chromatographic separation was carried out on Acquity UPLC w BEH phenyl C18 1.7 mm, 2.1 3 50 mm column. Drug elution was facilitated by using mobile phase containing acetonitrile (0.1% glacial acetic) and water (pH 3.5), in a ratio of 75 : 25, flowing at 0.2 mL/min. Molecular ions were generated by using the positive electrospray ionization mode (ESI 1) and analyzed on a triple-quadrupole mass spectrometer. The ionic transitions of diclofenac (m/z 296 > 214 and 249.9) and flufenamic acid (internal standard) (m/z 282.1 > 166.9 and 244) were measured in multiple reaction modes. Developed method is simple, quick, precise and accurate over a linearity range of 80-4,000 ng/mL. The lower limit of quantification (LLOQ) for diclofenac was 80 ng/mL. The percentage recoveries of diclofenac at three quality control samples were 54
This work describes a simple, sensitive, rapid and economical analytical procedure for direct spectrophotometric evaluation of diclofenac sodium (DS) using aqueous medium without using a chemical reagent. Parameters like time, temperature, acidic and basic conditions and interference by analgesic drugs were studied for a 5µg ml-1 solution of DS at 276 nm. Under optimized parameters, a linear working range of 0.1-30 µg ml-1 with regression coefficient of 0.9998 and lower detection limit of 0.01 µg ml-1 was obtained. The method was applied for DS contents in tablets, serum and urine samples.
Journal of Pharmacy and Chemistry, 2010
A fast, sensitive and specific LC-MS/MS method for the determination of Aceclofenac in human plasma has been developed and validated over the range of 0.106 μg/ml to 14.060 μg/ml (r2 >0.999). Samples (200 μL) were buffered (pH 6.8), extracted using acetonitrile and 5 μL of sample extract was injected into the LC-MS/MS system. Analysis was performed using anal micro C18 (4.6 X 50 mm, 50μm, 60AO) column by gradient elution at a flow rate of 0.350 ml/min over a 2min’s run-time. Retention times of Aceclofenac and Diclofenac (Internal Standard) were observed at 1.20 and 1.21 min’s respectively. Detection was achieved by using Thermo, Triple Quadruple mass spectrometer, in positive electro spray ionization mode. Ion transitions were monitored using MRM (multiple reaction monitoring) for drug (m/z 354 –> 250) and for IS (m/z 296.1 –> 215). This validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies.
Journal of Chromatography B: Biomedical Sciences and Applications, 1989
sodium, sodmm o-(2,6-dlchlorophenyl )ammophenylacetate (Voltaren 1, 1s a potent non-steroidal anti-inflammatory and analgesic drug, which has been used successfully for several years m the treatment of rheumatic deseases [l-3] This compound 1s metabolized m animals and humans to the corresponding mono-and dlhydroxy and conjugated derlvatlves [4,5] Several methods have been described for its determmatlon m body flulds, includmg gas chromatography with electron-capture detection [ 6,7], gas chromatography-mass spectrometry and high-performance llquld chromatography (HPLC) with VV detection [lo-21
Studia Universitatis Babeș-Bolyai Chemia, 2019
The purpose of this study was the development and validation of an LC-MS/MS method, for the determination of diclofenac from human plasma. The sample workup involved a simple protein precipitation procedure. A core/shell type analytical column (50×2,1 mm, 2.6 Å) was used with C18 stationary phase. The mobile phase consisting of 52.5% acetonitrile and 47.5% water provided good peak shape, accuracy and precision (stable ionization). The mass spectrometer was operated in negative electrospray ionization mode for analyte and internal standard. The following parameters were evaluated for validation purpose: Selectivity, sensitivity, matrix effect, anticoagulant effect, linearity, precision and accuracy, recovery, short and long term analyte/IS stability in solvent/matrix and carryover. The validated calibration range was 3.9-1194 ng/ml. The correlation coefficient R 2 was at least 0.999 in all validation batches. The validated method has been successfully used for the evaluation of bioequivalence of a generic diclofenac potassium formulation of 12.5 mg strength.
Biological Mass Spectrometry, 1988
A sensitive and reliable gas chromatography/mass spectrometric assay for diclofenac in plasma using selected ion monitoring is described. The procedure is based on the acidic extraction of diclofenac and ketoprofen (internal standard) with toluene. Both compounds are converted into their ethyl ester derivatives with ethanol containing 05% (v/v) sulphuric acid. No internal cyclization to indolone side product is produced in these conditions. The ions monitored are m / t 214 for diclofenac and m/z 209 for ketoprofen. The main recovery of diclofenac added to plasma has been estimated around 84.6% (120 ng mi-', n = 4). The intra-assay and inter-assay variability were 1.9% and 10.3%, respectively. The sensitivity was lower than 2 ng mi-'. The applicability of the assays to study the bioavailability of two formulations in a multipledosage trial is described. The method has been used in more than 600 determinations without any interference. Ion 214.00 amu. from M11 '0°1 3 7 9