Analytical Method Development and Validation for Simultaneous Estimation of Naproxen and Esomeprazole Magnesium in Tablet Dosage form by RP-HPLC

INTRODUCTION: Analytical chemistry, like other areas of chemistry and science, has gone through drastic changes and growth. Analytical chemistry may defined as the “Science and art of determining the composition of materials in terms of the elements or compounds contained”. In analytical chemistry it is of prime importance to gain information about the qualitative and quantitative composition of substances and chemical species, that is to find out what a substance is composed of and exactly how much . Analytical method is a specific application of a technique to solve an analytical problem. The use of instrumentation is an exciting and fascinating part of chemical analysis that interacts with all areas of chemistry and with many other areas of pure and applied science. Analytical instrumentation plays an important role in the production and evaluation of new products and in the protection of consumers and the environment. This instrumentation provides the lower detection limits required to assure safe foods, drugs and water. The manufacture of materials, whose composition must be known precisely such as substances used in integrated circuit chips, is monitored by analytical instruments. Instrumental or physicochemical methods are based on the theory of relations between the content and the corresponding physicochemical and physical properties of the chemical system being analyzed. Changes in the system properties are either detected or recorded through the measurement of current, electrode potential, electrical conductivity, optical density, refractive index etc. with suitable and sensitive instruments. In instrumental analysis physical property of substance is measured to determine its chemical composition. Measurements of physical properties of analyte such as conductivity, electrode potential, light absorption or emission, mass to charge ratio, and fluorescence, began to be used for quantitative analysis of variety of inorganic and biochemical analyses. Highly efficient chromatographic and electrophoretic techniques began to replace distillation, extraction, and precipitation for the separation of components of complex mixtures prior to their qualitative or quantitative determination. AIM: To develop and validate the method for simultaneous estimation of Naproxen and Esomeprazole magnesium by RP-HPLC. OBJECTIVES: On literature survey it was found that Naproxen and Esomeprazole magnesium is estimated by HPLC and UV Spectrophotometric methods, in combination with other drugs in tablet and bulk dosage form. However no method could be found for simultaneous estimation of Naproxen and Esomeprazole magnesium, and also no method was available for such estimation in the pharmacopoeia. In view of the need for a suitable method for routine analysis of Naproxen and Esomeprazole magnesium in formulations, attempts are being made to develop simple, precise and accurate analytical methods for simultaneous estimation of Naproxen and Esomeprazole magnesium and extend it for their determination in formulations. The utility of the developed methods to determine the content of both drugs in commercial tablet is also demonstrated. Validation of the method was done in accordance with USP and ICH guidelines for the assay of active ingredients. The methods were validated for parameters like accuracy, linearity, precision, specificity, ruggedness, robustness, and system suitability. These methods provide means to separate the individual components of a mixture and simultaneously characterize and quantify the components. These proposed methods are suitable for the pharmaceutical analysis in analytical laboratories. The Chromatographic methods proposed in this presume that there is a linear relationship between absorbance and component concentration. These methods have a calibration step followed by the prediction step, in which the results of the calibration step are used to estimate the component concentration from an unknown sample spectrum. The Chromatographic methods have many of full spectrum advantages. These methods are known to provide additional advantages that calibration can be performed by ignoring the concentration of all other components except the analyte of interest. These methods have been successfully applied to the quantitative analysis in spectrophotometric, chromatographic and electrochemical data. In summary, the primary objective of proposed work is to:- 1. Develop new, simple, sensitive, accurate, and economical analytical methods for the simultaneous estimation of Naproxen and Esomeprazole magnesium. 2. Validate the proposed methods in accordance with USP and ICH guidelines for the intended analytical application i.e., to apply the proposed method for analysis of these drugs in their combined dosage form. RESULT AND DISCUSSION: The objective of the proposed work was method development for the simultaneous estimation of Naproxen and Esomeprazole magnesium in tablets by RP-HPLC and to validate the developed method according to USP and ICH guidelines and applying the same for use in the quality control samples in pharmaceutical industry. As there is no official method for the simultaneous estimation of Naproxen and Esomeprazole magnesium in this selective combination, so we tried to develop a method by which we can quantify the amount of drug present in the given sample. In RP-HPLC method, the conditions were optimized to obtain an adequate separation of eluted compounds. Initially, various mobile phase compositions were tried, to separate titled ingredients. Mobile phase and flow rate selection was based on peak parameters (height, tailing, theoretical plates, capacity or symmetry factor), run time and resolution. The system with pH7.3 Phosphate Buffer: ACN: Water (50:35:15) at flow rate of 1.0 ml/min was found to be quite robust. The optimum wavelength for detection was 302 nm at which better detector response for both the drugs was obtained. The average retention times for Naproxen and Esomeprazole magnesium was found to be 3.397 and 8.146 min, respectively. According toUnited States Pharmacopeia, system suitability tests are an integral part of chromatographic method. They are used to verify the reproducibility of the chromatographic system. To ascertain its effectiveness, system suitability tests were carried out on freshly prepared stock solutions. The calibration was linear in various concentration range with correlation. The low values of RSD indicate that the method was precise and accurate. The mean recoveries were found in the range of 98 – 102 %. System precision is evaluated by injecting 6 injections of standard solution and low value of % RSD shows that system is precise. Precision for method is evaluated by analyzing a sample of homogenous batch six times and the low % RSD value shows the method is precise. Method robustness was evaluated by alteration of flow rate (±0.2 mL), Wavelength (± 2 nm), Mobile phase Organic Content (±5%) and it was found robust as % RSD was below 2.0%. Ruggedness of the proposed method was determined by analysis of aliquots from homogeneous slot in different laboratories, by different analysts, different column, different system using similar environmental conditions, the % R.S.D. reported was found to be less than 2 %. The proposed method was validated in accordance with ICH parameters and the applied for analysis of the same in marketed formulations. Both sample solution and standard solution are stable at 25°C for 24 hrs. as the % difference in the RSD was found to be less than 2.0%. Finally, it can be concluded that the assay values of formulation were the same as mentioned in the label claim with the RSD of ≤ 2.0%. The proposed method was found to be accurate, precise, reproducible and stable, and can be successfully applied for the routine analysis of both the drugs in combined tablet dosage forms. CONCLUSION: An efficient high performance liquid chromatographic method was developed and validated for the simultaneous estimation of Naproxen and Esomeprazole magnesium. In RP-HPLC method, the conditions were optimized to obtain an adequate separation of eluted compounds. Initially, various mobile phase compositions were tried, to separate titled ingredients. Mobile phase and flow rate selection was based on peak parameters (height, tailing, theoretical plates, capacity or symmetry factor), run time and resolution. The system with pH 7.3 Phosphate buffer: ACN: Water at flow rate of 1.0 mL/min was found to be quite robust. The low values of RSD indicate that the method was precise and accurate. The mean recoveries were found in the range of 98 – 102 %. System precision is evaluated by injecting 6 injections of standard solution and low value of % RSD shows that system is precise. Precision for method is evaluated by analysing a sample of homogenous batch six times and the low % RSD value shows the method precise

Measuring maternal mortality : an overview of opportunities and options for developing countries

Background:There is currently an unprecedented expressed need and demand for estimates of maternal mortality in developing countries. This has been stimulated in part by the creation of a Millennium Development Goal that will be judged partly on the basis of reductions in maternal mortality by 2015. Methods: Since the launch of the Safe Motherhood Initiative in 1987, new opportunities for data capture have arisen and new methods have been developed, tested and used. This paper provides a pragmatic overview of these methods and the optimal measurement strategies for different developing country contexts. Results: There are significant recent advances in the measurement of maternal mortality, yet also room for further improvement, particularly in assessing the magnitude and direction of biases and their implications for different data uses. Some of the innovations in measurement provide efficient mechanisms for gathering the requisite primary data at a reasonably low cost. No method, however, has zero costs. Investment is needed in measurement strategies for maternal mortality suited to the needs and resources of a country, and which also strengthen the technical capacity to generate and use credible estimates. Conclusion: Ownership of information is necessary for it to be acted upon: what you count is what you do. Difficulties with measurement must not be allowed to discourage efforts to reduce maternal mortality. Countries must be encouraged and enabled to count maternal deaths and act.WJG is funded partially by the University of Aberdeen. OMRC is partially funded by the London School of Hygiene and Tropical Medicine. CS and SA are partially funded by Johns Hopkins University. CAZ is funded by the Health Metrics Network at the World Health Organization. WJG, OMRC, CS and SA are also partially supported through an international research program, Immpact, funded by the Bill & Melinda Gates Foundation, the Department for International Development, the European Commission and USAID

What Can We Conclude from Death Registration? Improved Methods for Evaluating Completeness

Julie Rajaratnam and colleagues evaluate the performance of a suite of demographic methods that estimate the fraction of deaths registered and counted by civil registration systems, and identify three variants that generally perform the best

Prospective functional classification of all possible missense variants in PPARG.

Clinical exome sequencing routinely identifies missense variants in disease-related genes, but functional characterization is rarely undertaken, leading to diagnostic uncertainty. For example, mutations in PPARG cause Mendelian lipodystrophy and increase risk of type 2 diabetes (T2D). Although approximately 1 in 500 people harbor missense variants in PPARG, most are of unknown consequence. To prospectively characterize PPARγ variants, we used highly parallel oligonucleotide synthesis to construct a library encoding all 9,595 possible single-amino acid substitutions. We developed a pooled functional assay in human macrophages, experimentally evaluated all protein variants, and used the experimental data to train a variant classifier by supervised machine learning. When applied to 55 new missense variants identified in population-based and clinical sequencing, the classifier annotated 6 variants as pathogenic; these were subsequently validated by single-variant assays. Saturation mutagenesis and prospective experimental characterization can support immediate diagnostic interpretation of newly discovered missense variants in disease-related genes.This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (1K08DK102877-01, to A.R.M.; 1R01DK097768-01, to D.A.), NIH/Harvard Catalyst (1KL2TR001100-01, to A.R.M.), the Broad Institute (SPARC award, to A.R.M. and T.M.), and the Wellcome Trust (095564, to K.C.; 107064, to D.B.S.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.370

A Protocol for the Secure Linking of Registries for HPV Surveillance

In order to monitor the effectiveness of HPV vaccination in Canada the linkage of multiple data registries may be required. These registries may not always be managed by the same organization and, furthermore, privacy legislation or practices may restrict any data linkages of records that can actually be done among registries. The objective of this study was to develop a secure protocol for linking data from different registries and to allow on-going monitoring of HPV vaccine effectiveness.A secure linking protocol, using commutative hash functions and secure multi-party computation techniques was developed. This protocol allows for the exact matching of records among registries and the computation of statistics on the linked data while meeting five practical requirements to ensure patient confidentiality and privacy. The statistics considered were: odds ratio and its confidence interval, chi-square test, and relative risk and its confidence interval. Additional statistics on contingency tables, such as other measures of association, can be added using the same principles presented. The computation time performance of this protocol was evaluated.The protocol has acceptable computation time and scales linearly with the size of the data set and the size of the contingency table. The worse case computation time for up to 100,000 patients returned by each query and a 16 cell contingency table is less than 4 hours for basic statistics, and the best case is under 3 hours.A computationally practical protocol for the secure linking of data from multiple registries has been demonstrated in the context of HPV vaccine initiative impact assessment. The basic protocol can be generalized to the surveillance of other conditions, diseases, or vaccination programs

Fracture dislocation of scaphoid in association with polytrauma: Diagnostic and management considerations

Isolated fracture of the scaphoid with the dislocation of the proximal bony component is a rare abnormality, usually encountered in a high-energy injury. Prompt diagnosis is essential for preferentially considering open reduction and fixation. Careful image analysis is necessary to exclude more frequent injuries such as lunate dislocation and establish encroachment of carpal tunnel or injury to median nerve. This presentation presents imaging and management consideration of the patient with the scaphoid fracture with dislocation of proximal component encountered in association with polytrauma

Student Pharmacists during the Pandemic: Development of a COVID-19 Knowledge, Attitudes, and Practices (COVKAP) Survey

Background: The COVID-19 pandemic has caused innumerable changes to all aspects of human life and behavior, including academic life. This study describes the development of a COVID-19 Knowledge, Attitudes, and Practices (COVKAP) Survey among U.S. student pharmacists. The survey was administered at Doctor of Pharmacy programs in three states—Tennessee, Ohio, and Pennsylvania. Methods: The COVKAP survey—an online cross-sectional survey—was distributed to U.S. student pharmacists enrolled in three different colleges of pharmacy in three states during the fall semester of 2020. The survey was developed using literature review and Dillman’s recommendations for survey design. The COVKAP survey consisted of 23 closed and Likert-scale questions, and three open-ended questions. The research team conducted descriptive and inductive thematic analyses on the quantitative and qualitative data, respectively using SPSS (v27) and Dedoose® software. Results: A total of 421 responses were received. Respondents were predominantly female (72%) and White (79%). The average age of respondents was 23.4 years. The qualitative analysis revealed three themes: (1) Wellbeing and mental health struggles; (2) Being part of the decision-making process; (3) Necessity of adequate protection measures. Conclusions: Preliminary study findings indicate that student pharmacists’ concerns and the challenges that they face in their academic pursuits are largely similar across the three states in this study and inform about the importance of recognizing and mitigating the impact of widespread disruption in education. This disruption provides an opportunity for pharmacy academia to examine practices and methods that can be improved upon to help students become successful practitioners

Student Pharmacists during the Pandemic: Development of a COVID-19 Knowledge, Attitudes, and Practices (COVKAP) Survey

Background: The COVID-19 pandemic has caused innumerable changes to all aspects of human life and behavior, including academic life. This study describes the development of a COVID-19 Knowledge, Attitudes, and Practices (COVKAP) Survey among U.S. student pharmacists. The survey was administered at Doctor of Pharmacy programs in three states—Tennessee, Ohio, and Pennsylvania. Methods: The COVKAP survey—an online cross-sectional survey—was distributed to U.S. student pharmacists enrolled in three different colleges of pharmacy in three states during the fall semester of 2020. The survey was developed using literature review and Dillman’s recommendations for survey design. The COVKAP survey consisted of 23 closed and Likert-scale questions, and three open-ended questions. The research team conducted descriptive and inductive thematic analyses on the quantitative and qualitative data, respectively using SPSS (v27) and Dedoose® software. Results: A total of 421 responses were received. Respondents were predominantly female (72%) and White (79%). The average age of respondents was 23.4 years. The qualitative analysis revealed three themes: (1) Wellbeing and mental health struggles; (2) Being part of the decision-making process; (3) Necessity of adequate protection measures. Conclusions: Preliminary study findings indicate that student pharmacists’ concerns and the challenges that they face in their academic pursuits are largely similar across the three states in this study and inform about the importance of recognizing and mitigating the impact of widespread disruption in education. This disruption provides an opportunity for pharmacy academia to examine practices and methods that can be improved upon to help students become successful practitioners