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According to current regulatory guidelines, a stability-indicating method has been developed to determine the impurities in sacubitril (SCB) and valsartan (VLS) tablet dosage forms and perform robustness studies using the design of experiments approach. The present study was initiated to understand quality target product profile, analytical target profile, and risk assessment for method variables that affect the method response. A reversed-phase-HPLC system was equipped with a Phenomenex Gemini-NX C 18 column (150 Â 4.6 mm, 3 μm) and a photo diode array detector. A gradient mobile phase was used in this research work. The detection was performed at 254 nm; the flow rate was 1.5 mL/min, and the column temperature was maintained at 30 C. The proposed method was validated per the International Council for Harmonisation Q2 (R1) guidelines. The coefficient of correlation was >0.999 for all impurities. The limits of detection and quantification were evaluated for SCB, VLS, and all impurities. The precision and accuracy were obtained for SCB, VLS, and their related impurities. Intra-and inter-day relative standard deviation values were less than 10.0%, and the recoveries of impurities varied between 90.0 and 115.0%.Based on the validation results, the proposed DoE method can estimate SCB and VLS impurities in the finished dosage form. K E Y W O R D S design of experiments, impurities, reversed-phase-HPLC, sacubitril, valsartan 1 | INTRODUCTION Currently, the combination of sacubitril (SCB) and valsartan (VLS) tablets is used to treat anti-hypertensive. Sacubitril sodium is chemically designated as 4-[[(2S, 4R)-5-ethoxy-4-methyl-5-oxo-1-(4-biphenylyl) pentan-2-yl] amino]-4-oxobutanoate. The molecular formula of SCB is C 24 H 29 NO 5 , and its molecular weight is 411.49 g/mol. SCB is used to treat cardiac hypertension. It is a prodrug that is activated to SCB at LBQ657 by de-ethylation via esterases. SCB inhibits the enzyme neprilysin. Neprilysin degrades atrial and brain natriuretic peptides, two blood pressure (BP)-lowering peptides, mainly reducing blood volume. In addition, neurolysin degrades various peptides, including bradykinin, an inflammatory mediator exerting potent vasodilator action. According to biopharmaceutics classification system study, it is a class II drug (low solubility and high permeability). It contains one Abbreviations used: DoE, design of experiments; OFAT, one factor at a time; QbD, quality by design; RSD, relative standard deviation.

This study reviews the need and importance of non-aqueous dyeing systems in the chemical processing industry, especially using the reverse micellar system in the dyeing of natural fibres. When it comes to conventional dyeing systems, which use large quantities of water, chemical, and energy, cause a lot of effluent load to the environment. Again the effluent water has to be treated well to eliminate all the harmful substances in it. To overcome the issues, a lot of research has been carried out in this area to minimise the use of water and chemicals in the dyeing process. Like use of low material to liquor ratio (M:L) in dyeing, dyes with high fixation at lower temperatures, low/salt less dyeing in case of reactive dyeing with cotton, cottonseed oil dyeing, microwaveassisted dyeing, and use of supercritical carbon dioxide in case of polyester dyeing and many more. All the above said methods are aqueous-based and, after the completion of dyeing, results in wastewater generation, which requires further treatment to reduce the harmful chemicals. Therefore, to further minimise the use of water and chemicals in the dyeing of natural fibres reverse micellar system has been introduced with the help of surfactants of both Ionic and nonionic in nature. As of today, a lot of work has been carried out in the dyeing of natural fibres with this system by employing ionic, nonionic, and mixed surfactants. Fascinating results were obtained in the dyeing with good levelness, high exhaustion, and fixation values, and results were compared with conventional dyeing. Computer colour matching studies were also done better to understand the applicability of these systems in the industry and found nearer results.

A highly sensitive liquid chromatography–tandem mass spectrometry method was developed to estimate azathioprine in presence of its active metabolite mercaptopurine in human plasma. The analyte and isotope‐labeled internal standards were extracted from 300 μL human plasma by a solid‐phase extraction technique. The method was revealed good linearity over a concentration range of 0.151 to 49.500 ng/mL for azathioprine, containing 50.000 ng/mL of mercaptopurine in all the quality control samples. The detection was established using multiple reaction monitoring method. The method validation was carried out as per the present guidelines on bioanalytical method validation of European medicines agency and United States Food and Drug Administration. The current method was successfully applied to study the pharmacokinetics of azathioprine 50 mg tablets on healthy human volunteers. The results of pharmacokinetic parameters have demonstrated that, estimation of azathioprine in presence of mercaptopurine has no impact on azathioprine results.

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