Simple and Fast Liquid Chromatography–Mass Spectrometry (LC–MS) Method for the Determination of Omeprazole, 5-hydroxyomeprazole, and Omeprazole Sulphone in Human Plasma (original) (raw)
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Effect of Omeprazole on the Pharmacokinetics of Rosuvastatin in Healthy Male Volunteers
American Journal of Therapeutics, 2016
The current study aimed at the evaluation of, in vivo, the effect of omeprazole on the pharmacokinetics of rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. Omeprazole is an acid suppressant and CYP2C9, CYP3A4, and CYP2C19 substrate and inhibitor, as well as inhibitor of transporters (like P-gp). This was a randomized, open-label, 2-period, crossover study. Healthy male volunteers (N 5 20), divided into 2 groups, were given single oral doses of rosuvastatin 40 mg either alone (treatment period I) or concomitantly with omeprazole 40-mg capsule (treatment period II). Plasma concentrations of rosuvastatin (rosuva) and its metabolite N-desmethyl rosuvastatin (NDM-rosuva) were quantified by a validated liquid chromatographytandem mass spectrometry method developed in our laboratory. An insignificant decrease (P. 0.05) has been observed in the values of maximum plasma concentrations, clearance, and half-life of rosuva, whereas an insignificant increase (P. 0.05) has been observed in the area under the plasma concentration-time curves from zero time to the last measurable concentration½AUC t 0 , that extrapolated to infinity ½AUC N 0 , and mean residence time values after concomitant administration with omeprazole. Although omeprazole concomitant administration altered the pharmacokinetics of NDM-rosuva metabolite significantly, rosuva's very little metabolism (10%) suggests that these changes are of no clinical significance. Concomitant administration of omeprazole with rosuva did not alter the pharmacokinetics of rosuva in healthy volunteers. These data are consistent with other reported studies, indicating that rosuva is not a good candidate for metabolism-based drug-drug interactions. Therefore, rosuva can be administered safely along with omeprazole.
Biomedical Chromatography, 2006
A specific, accurate, precise and reproducible high-performance liquid chromatography (HPLC) method was developed for the estimation of rosuvastatin (RST), a novel, synthetic and potent HMG-CoA inhibitor in rat plasma. The assay procedure involved simple liquid-liquid extraction of RST and internal standard (IS, ketoprofen) from a small plasma volume directly into acetonitrile. The organic layer was separated and evaporated under a gentle stream of nitrogen at 40°C. The residue was reconstituted in the mobile phase and injected onto a Kromasil KR 100-5C 18 column (4.6 × 250 mm, 5 µm). Mobile phase consisting of 0.05 M formic acid and acetonitrile (55:45, v/v) was used at a flow rate of 1.0 mL/min for the effective separation of RST and IS. The detection of the analyte peak was achieved by monitoring the eluate using a UV detector set at 240 nm. The ratio of peak area of analyte to IS was used for quantification of plasma samples. Nominal retention times of RST and IS were 8.6 and 12.5 min, respectively. The standard curve for RST was linear (r 2 > 0.999) in the concentration range 0.02-10 µg/mL. Absolute recoveries of RST and IS were 85-110 and >100%, respectively, from rat plasma. The lower limit of quantification (LLOQ) of RST was 0.02 µg/mL. The inter-and intra-day precisions in the measurement of quality control (QC) samples, 0.02, 0.06, 1.6 and 8.0 µg/mL, were in the range 7.24-12.43% relative standard deviation (RSD) and 2.28-10.23% RSD, respectively. Accuracy in the measurement of QC samples was in the range 93.05-112.17% of the spiked nominal values. Both analyte and IS were stable in the battery of stability studies, viz. benchtop, autosampler and freeze-thaw cycles. RST was found to be stable for a period of 30 days on storage at −80°C. The application of the assay to determine the pharmacokinetic disposition after a single oral dose to rats is described.
sphinxsai.com
Two new, simple, sensitive and accurate stability-indication methods were developed for quantitative determination of rosuvastain in the presence of its degradation products in raw material. The first is a High-Performance Liquid Chromatography (HPLC) method in which separation was achieved on Phenomenex C 18 column (250 mm, i.d. 4.6 mm, 5 µm) using acetonitrile: 0.5 % formic acid (50 + 50, v/v) as the mobile phase at a flow rate of 1.0 mL/min at ambient temperature (22-27 °C) with ultraviolet detection at 248 nm over a concentration range of 5-300 µg/ml with mean recovery of 99.51-100.66 %. The second method is High-Performance Thin Layer Chromatography (HPTLC) in which the drug is separated form its acidic degradation products on silica gel 60F 254 plates using ethylacetate: toluene: acetonitrile: formic acid (6 + 3.5 + 0.5 + 0.2 v/v/v/v) as the mobile phase with ultraviolet detection of the separated bands at 243 nm over a concentration range of 318-3816 ng/spot for rosuvastain with mean recovery 99.77-101.94 %. Both methods can analysis Rosuvastatin in bulk drug with intraday and interday precision of 0.23-0.87% and 0.29-0.84%, respectively for HPLC method and 0.48-0.93 % and 0.24-0.77 %, respectively for HPTLC method. Developed methods can apply for the estimation of three strength of NOVASTAT tablet manufacture by Lupin pharmaceuticals.
Journal of Bioequivalence & Bioavailability, 2014
Reference standards of Rosuvastatin (purity 99%) and Ezetimibe (purity 99.5%) were obtained from Glenmark Pharmaceuticals Ltd., India. The combination of Rosuvastatin and Ezetimibe is available as film-coated tablets (10 mg of Rosuvastatin and 10 mg of Ezetimibe) with brand names RAZEL-EZ ® (Glenmark Pharmaceuticals Ltd., India) and ROSUVAS-EZ ® (Ranbaxy Laboratories Ltd., India) and were procured from the local pharmacy store. Acetonitrile (HPLC grade), tetra butyl ammonium hydrogen sulphate (TBAHS) sodium hydroxide and hydrochloric acid and hydrogen peroxide were purchased from Merck (India). Tetra butyl ammonium hydrogen sulphate buffer (pH 3.4) solution The mobile phase was prepared by accurately transferring 3.3954 g of TBAHS in to a 1000 mL volumetric flask and dissolved with HPLC grade water.
A simple reversed-phase high-performance liquid chromatographic (RP-HPLC) method has been developed and validated for simultaneous determination of Rosuvastatin and Ezetimibe in pharmaceutical tablet dosage form. Chromatographic analysis was performed on a Symmetry X-terra C8 (4.6mm x 100mm, 5m)column at ambient temperature with a mixture of ortho phosphoric acid buffer and Acetonitrile in the ratio 40:60 v/v as mobile phase, at a flow rate of 1.0 mL min-1. UV detection was performed at 237 nm.. The retention times of Rosuvastatin and Ezetimibe were 2.490 and 3.173 min, respectively. The correlation coefficient of Rosuvastatin and Ezetimibe was found to be 0.999. Calibration plots were linear over the concentration ranges 10-50 μg mL-1 for Rosuvastatin and Ezetimibe, respectively. The Limit of detection was 1.626 and 0.918µg mL-1 and the quantification limit was 4.927 µg mL-1 and 2.783µg mL-1 for Rosuvastatin and Ezetimibe, respectively. The accuracy of the proposed method was dete...
Pharmacokinetic study of rosuvastatin in males and females
European Journal of Drug Metabolism and Pharmacokinetics, 2014
Rosuvastatin is used to treat dyslipidemia and is metabolized by CYP2C9 that shows variable metabolic activity in males and females. Pharmacokinetics (PK) of drugs varies in males and females that may result in altered drug response and therapeutic efficacy. In current study, PK of rosuvastatin has been evaluated in males and females. A single oral dose (40 mg rosuvastatin), openlabel and non-controlled PK study was arranged. A reversed phase HPLC method was applied for quantification of rosuvastatin in serum samples. PK parameters of rosuvastatin were compared in males and females by applying student t test at 95 % confidence interval. The C max , ½AUC 8 0 and ½AUC 1 0 of rosuvastatin was significantly higher (p \ 0.05) in females compared with males. The Vd/F of rosuvastatin was insignificantly higher (p [ 0.05) in males compared with females while CL/F was significantly (p \ 0.05) faster in males when compared at 95 % confidence interval. Rosuvastatin plasma level was significantly high in females compared with males that may be a possible reason for higher incidence of cardiac myopathy and other side effects in females. The variation in PK of drugs in males and females may require dose adjustment for maximum therapeutic effectiveness and safety.
LC determination of Rosuvastatin and Ezetimibe in Human plasma
A simple, precise, sensitive and validated reverse-phase high performance liquid chromatographic (RP-HPLC) method was developed for the simultaneous estimation of rosuvastatin and ezetimibe in human plasma. The method involved protein precipitation and extraction of both drugs from plasma using acetonitrile and then separation on a C-18 column. Both the analytes were detected at a wavelength of 240 nm using diode array detector. Mobile phase for the said separation consists of a mixture of 1.5% phosphoric acid and acetonitrile in 30:70, v/v ratio. Linearity was in the range of 0.32-267 mg/mL for rosuvastatin and 0.08-67 mg/mL for ezetimibe with coefficient of determination between 0.9997 and 0.9967. Limit of detection was 0.106 mg/mL for rosuvastatin and 0.026 mg/mL for ezetimibe whereas limit of quantification was 0.32 mg/mL and 0.08 mg/mL for rosuvastatin and ezetimibe respectively. Recovery of both the analytes was greater than 75% with RSD less than 15 %. The total run time was less than five min for the two components. The developed method can be fruitfully employed for the determination of these two drugs in human plasma.
Journal of the Brazilian Chemical Society, 2005
Um método empregando LC-MS/MS foi desenvolvido para a análise de rosuvastatina em plasma humano, usando atorvastatina como padrão interno. Rosuvastatina é um fármaco para redução de lipídeos e prescrita para o tratamento do hipercolesterolemia e de dislipidimia. A extração em fase sólida (SPE) foi usada para purificação e pré-concentração do analito a partir da matriz do plasma humano. A separação cromatográfica foi conseguida em 6.0 min empregando fase móvel composta de 0.2% de ácido fórmico em água e acetonitrila (40: 60,v/v, na vazão de 1.0 mL min-1 e coluna YMC J'sphere ODS H-80, 150 x 4.6 mm, partículas de 4.0 μm. Na saída da coluna, a fase móvel foi dividida, sendo que 200 μL foram dirigidos para o espectrômetro de massas e 800 μL para o descarte. Pelo Monitoramento de Reação Múltipla (MRM), as transições foram medidas no modo positivo em m/z 482-258 para rosuvastatina e m/z 559-440 para o padrão interno, respectivamente. Uma validação detalhada do método foi realizada seguindo as recomendações do FDA americano e as curvas analíticas foram lineares no intervalo de 1.00 ng mL-1 a 50.00 ng mL-1 com coeficiente de correlação médio maior que 0.99. A recuperação absoluta foi maior que 50.14% para rosuvastatina e 54.65% para o padrão interno. Rosuvastatina foi estável por 138 dias a-70 ± 5 °C e por 24 horas à temperatura ambiente. Após a extração do plasma, as amostras reconstituídas de rosuvastatina permaneceram estáveis no auto injetor, a 10 °C, por 8 horas. Depois de submetidas a três ciclos de congelamento/descongelamento, não houve mudanças na recuperação do analito. O método é simples, específico, sensível, preciso, exato e apropriado para aplicações em bioequivalência e estudos farmacocinéticos. Foi aplicado com sucesso em um estudo piloto de bioequivalência da rosuvastatina, comprimidos-Zydus, Cadila, India versus comprimidos-Crestor, Astra Zeneca, EUA, em voluntários sadios do sexo masculino. A LC-MS/MS method has been developed for the estimation of rosuvastatin in human plasma using atorvastatin as internal standard. Rosuvastatin is a lipid-lowering drug prescribed for the treatment of hyper-cholestrolemia and dyslipidimia. Solid phase extraction (SPE) was used for the purification and pre-concentration of analyte from human plasma matrix. The chromatographic separation was achieved within 6.0 min by an isocratic mobile phase containing 0.2% formic acid in water and acetonitrile (40: 60, v/v), flowing through YMC J' Sphere ODS H-80, 150 x 4.6 mm, 4.0 μm analytical column, at a flow rate of 1.0 mL min-1 with split of 200 μL to mass spectrometer and 800 μL to waste. Multiple reaction monitoring (MRM) transitions were measured in the positive mode at m/z 482 and 258 for rosuvastatin and m/z 559 and 440 for internal standard respectively. A detailed validation of the method was performed as per USFDA guidelines and the standard curves were found to be linear in the range 1.0 ng mL-1 to 50.0 ng mL-1 with the mean correlation coefficient more than 0.99. The absolute recovery was more than 50.14% for rosuvastatin and 54.65% for internal standard. In human plasma, rosuvastatin was stable for 138 days at-70 ± 5 °C and for 24 hours at ambient temperature. After extraction from plasma, the reconstituted samples of rosuvastatin were stable in auto sampler at 10 °C for 8 hours. Upon subjecting to three freeze thaw cycles, there was no change in the recovery of the analyte. The method was simple, specific, sensitive, precise, accurate and suitable for bioequivalence and pharmacokinetic studies. It was successfully applied to the pilot bioequivalence study of rosuvastatin 20 mg tablets of M/s Zydus Cadila health care Ltd. India versus 20 mg Crestor tablet of M/s Astra Zeneca, USA; in male human subjects.
Indian Drugs
A bio analytical method was developed with compatible mobile phase for estimation of drugs viz. rosuvastatin and ezetimibe, amlodipine and valsartan, lercanidipine and fluvastatin in human plasma. Liquid chromatographic system takes ample of time to stabilise and to attain equilibrium on changeover of mobile phase. Compatible mobile phase was beneficial to separate and estimate many drugs simultaneously; and saved time and solvent consumption. The technique was developed and equipped with reverse phase high performance liquid chromatograph (RP-HPLC), using RP - C18 column with UV detector. For estimation of all these drugs, the mobile phase [acetonitrile: acetate buffer pH 4.0 (pH adjusted with acetic acid)] was pumped at a flow rate of 0.8 mL min-1 in the ratio of 60:40 V/V and the eluents were monitored at 245 nm. The method was studied and validated as per ICH guidelines and US FDA guidelines for selectivity, specificity, accuracy and precision and stability study. All these drug...
Studia Universitatis Babeș-Bolyai Chemia
A new analytical procedure for rapid and selective derivatization of rosuvastatin directly in plasma into their corresponding methyl esters was developed for gas chromatography-mass spectrometry analysis. This work is the first method of selective derivatization of the carboxyl group from rosuvastatin to methyl ester. The lipids from plasma were extracted with heptane before derivatization. The methyl esters were obtained by reaction with methyl iodide in solution of dimethyl sulfoxide and in the presence of anhydrous potassium carbonate. The optimal conditions for selective methylation have been established. The derivatization was carried out in 2 min. The method was validated for the analysis of rosuvastatin in plasma. The methyl ester of rosuvastatin was identified by electron ionization mass spectrometry. The electron ionization mass spectrometer detector response was linear up to 300 ng/mL. The limit of detection and limit of quantification values in total ion chromatogram method were 0.4 ng/mL and 1.2 ng/mL, respectively.