Method For Determination Of Omeprazole Research Articles

Validation of RP-HPLC Method for Determination of Omeprazole in Dissolution Media and Application to Study in-vitro Release from Solid- SNEDDS

Background: Omeprazole has poor water solubility, is unstable in acidic solutions, and undergoes first pass metabolism which results in lowering its bioavailability. A solid Self-Nano Emulsifying Drug Delivery System (SNEDDS) was previously prepared to enhance its dissolution. Objective: Development and validation of a RP-HPLC method with UV detection for the determination of omeprazole in 0.1N HCl and in 0.01 M phosphate buffer (pH 7.4). Methods: Validation was according to the ICH Q2 (R1) guidelines in terms of linearity, accuracy and precision, lower limit of quantification, sensitivity, specificity, and robustness. The developed and validated method was used to study the in-vitro dissolution of the drug from the solid-SNEDDS, commercial products and of the unprocessed drug. The dissolution was studied in 500 ml of 0.1N HCl during the first 2 hours, and 900 mL of 0.01 M phosphate buffer (pH 7.4) during the last hour (37 ± 0.5 oC and 100 rpm). Results: The method was linear in the range 1-50 μg/ml, accurate and precise as indicated by the ANOVA test. It was specific to the drug and the pharmaceutical excipients did not affect the determination of its concentration. The method was robust to small changes in pH, composition, and flow rate of the mobile phase. The dissolution rate of omeprazole from the Solid-SNEDDS was faster than that from two commercial dosage forms and than the dissolution rate of the unprocessed drug. Conclusion: The method met the acceptance criteria and was applied successfully in studying the rate of dissolution of the drug.

Effect of Sijunzi Pills on Pharmacokinetics of Omeprazole in Beagle Dogs by HPLC-UV: A Herb-Drug Interaction Study.

A sensitive high-performance liquid chromatography (HPLC-UV) method for determination of omeprazole in beagle dog plasma was developed and to investigate the effect of Sijunzi pills (SJZPs) on the pharmacokinetics of omeprazole in beagle dogs. The beagle dog plasma was extracted with ethyl acetate and n-hexane under alkaline conditions. Omeprazole and internal standard (IS, fluconazole) were separated on an XDB-C18 column, and acetonitrile and 0.1% trifluoroacetic acid were used as the mobile phase. Omeprazole and IS were detected by using a diode array detector. This experiment adopts the experimental design of double-cycle self-control. In the first cycle (group A), six beagle dogs were given omeprazole 0.67 mg/kg orally in a single dose. In the second period (group B), the same six beagle dogs were orally given SJZPs 0.2 g/kg twice a day for 7 consecutive days, and then, omeprazole was orally given. At the different time points after omeprazole was given in the two periods, the blood samples were collected. The concentration of omeprazole was detected by the developed HPLC method. DAS 2.0 was used to calculate the pharmacokinetic parameters of omeprazole. Under the current experimental conditions, this UPLC method showed good linearity in the detection of omeprazole. Interday and intraday precision did not exceed 10%, and the range of accuracy values were from −1.43% to 2.76%. The results of extraction recovery and stability met the requirements of FDA approval guidelines of bioanalytical method validation. The Cmax of omeprazole in group B was 61.55% higher than that in group A, and the AUC(0−t) and AUC(0−∞) of omeprazole in group B were 63.96% and 63.65% higher those that in group A, respectively. At the same time, the clearance (CL) and apparent volume of distribution (Vd) decreased in group B. In this study, an HPLC method for the determination of plasma omeprazole concentration was established. SJZPs could inhibit the metabolism of omeprazole and increase the concentration of omeprazole in beagle dogs. It is suggested that when SJZPs are combined with omeprazole, attention should be paid to the herb-drug interactions and possible adverse reactions.

A Validated High-Throughput Fluorometric Method for Determination of Omeprazole in Quality Control Laboratory via Charge Transfer Sensitized Fluorescence.

A high-throughput 96-microwell plate fluorometric method was developed and validated to determine omeprazole (OMZ) in its dosage forms. The method was based on the charge-transfer (CT) sensitized fluorescence reaction of OMZ with 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ). This fluorescence reaction provided a new approach for simple, sensitive and selective determinations of OMZ in pharmaceutical preparations. In the present method, the fluorescence reaction was carried out in 96-microwell plates as reaction vessels in order to increase the automation of the methodology and the efficiency of its use in quality control laboratories. All factors affecting the fluorescence reaction were carefully studied and the conditions were optimized. The stoichiometry of the fluorescence reaction between OMZ and DDQ was determined and the reaction mechanism was suggested. Under the optimum conditions, the linear range was 100-6000ng/ml with the lowest LOD of 33ng/ml. Analytical performance of the proposed assay, in terms of accuracy and precision, was statistically validated and the results were satisfactory; RSD was <2.6% and the accuracy was 98.6-101.6%. The method was successfully applied to the analysis of OMZ in its dosage forms; the recovery values were 98.26-99.60±0.95-2.22%. The developed methodology may provide a safer, automated and economic tool for the analysis of OMZ in quality control laboratories.

A New Ultra Performance Liquid Chromatographic Method for Determination of Omeprazole in Capsule Dosage Form

A New Ultra Performance Liquid Chromatographic Method for Determination of Omeprazole in Capsule Dosage Form

Quality by Design (QbD): A Practical Experimental Design Approach by Blocking and Varying Certain Factors of a Stability-Indicating HPLC Method for Simultaneous Determination of Omeprazole and Ketoprofen

This manuscript demonstrates a Quality by Design approach using Design of Experiments to prove the robustness of a stability indicating HPLC method. The method determines the omeprazole in the presence of eight related substances and ketoprofen with six impurities developed for pellets filled capsule as a combined finished drug product. Based on the results, controllable factors that have influential effect on the resolution between peaks were identified and were examined while blocking the uncontrollable factors. The design employs a full factorial design of experiment for the interaction of controllable factors. A flowchart parades all steps of QbD approach by blocking and varying certain factors. Thus, the primary objective of this manuscript is to demonstrate the method's robustness by clarifying various steps systematically.

New Sensitive Kinetic Spectrophotometric Methods for Determination of Omeprazole in Dosage Forms

New rapid, sensitive, and accurate kinetic spectrophotometric methods were developed, for the first time, to determine omeprazole (OMZ) in its dosage forms. The methods were based on the formation of charge-transfer complexes with both iodine and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The variables that affected the reactions were carefully studied and optimized. The formed complexes and the site of interaction were examined by UV/VIS, IR, and 1H-NMR techniques, and computational molecular modeling. Under optimum conditions, the stoichiometry of the reactions between OMZ and the acceptors was found to be 1 : 1. The order of the reactions and the specific rate constants were determined. The thermodynamics of the complexes were computed and the mechanism of the reactions was postulated. The initial rate and fixed time methods were utilized for the determination of OMZ concentrations. The linear ranges for the proposed methods were 0.10–3.00 and 0.50–25.00 μg mL−1 with the lowest LOD of 0.03 and 0.14 μg mL−1 for iodine and DDQ, respectively. Analytical performance of the methods was statistically validated; RSD was <1.25% for the precision and <1.95% for the accuracy. The proposed methods were successfully applied to the analysis of OMZ in its dosage forms; the recovery was 98.91–100.32% ± 0.94–1.84, and was found to be comparable with that of reference method.

Simultaneous Determination of Omeprazole and its Metabolites (5′‐Hydroxyomeprazole and Omeprazole Sulfone) in Human Plasma by Liquid Chromatography‐Tandem Mass Spectrometry

A method for the simultaneous determination of omeprazole (OME) and its two metabolites (5′‐hydroxyomeprazole (H‐OME) and omeprazole sulfone (OME‐S)) in human plasma is described. OME and its metabolites were extracted from plasma with phosphate buffer (pH 7.4) by using solid phase extraction system, Oasis HLB μ Elution plates, and the eluate was directly injected into LC‐MS/MS system. The analytes were chromatographed with a reversed‐phase column, XTerra MS C18 column (150×4.6 mm) and an HPLC mobile phase which consisted of a mixture of acetonitrile/water (45/55, v/v) containing 10 mM ammonium hydroxide (pH 8.0). A Sciex API 4000 tandem mass spectrometer equipped with a heated nebulizer atmospheric pressure chemical ionization interface was used as a detector and was operated in the positive ion mode. Multiple reaction monitorings using the precursor product ion combinations of m/z 346.2→198.2, 362.0→214.0, 362.0→150.0, and 349.2→201.0 were used to detect OME, H‐OME, OME‐S, and internal standard (OME‐d3), respectively. The method was validated in the concentration range of 1–1000 ng/mL plasma with adequate assay precision, accuracy, and reproducibility. This sensitive and selective method with a rapid and simple sample preparation procedure was applied to a clinical pharmacokinetic study of OME.