The Clinical Aspects of Saroglitazar and its Side Effects

The new substance element has been known as novel antidiabetic drug, eg: saroglitazar. saroglitazar is a medication used to treat type-2 diabetes. saroglitazar was known under the exchange name Lipaglyn, created by Zydus cadila. lipaglyn is the first drug approved to treat type-2diabetes mellitus by the drug controller general of India in june 2013. Lipaglyn is demonstrated for the patients experiencing diabetes dyslipidaemia. It is given once daily for treatment. Saroglitazar manages the lipid parameters just as glycemic control. [1] Keywords: Anti-diabetic, dual PPAR agonist, glitazar, hypertriglyceridemia, insulin sensitizer, Lipaglyn, AE’s (adverse effects)

Implementation of green analytical principles to develop and validate the HPLC method for the separation and identification of degradation products of Panobinostat, and its characterization by using LC-QTOF-MS/MS and its in-silico toxicity prediction using ADMET software

Panobinostat (PAN) is an inhibitor of histone deacetylase (HDAC) that has been granted approval by the US Regulator for the purpose of treating chronic lymphocytic leukemia. Stress studies were conducted on PAN to assess its inherent stability under physical (thermal and photolytic) and chemical conditions (acidic, basic, neutral, and oxidative) in diluent (water: ethanol 50:50 v/v). The developed HPLC method exhibits both selectivity and specificity towards PAN and its degradation products (DPs). PAN and DPs were resolved using a Waters Xbridge C18 3.0 μm (50 × 4.6 mm) column. The mobile phase consisted of a gradient program (0/15, 2/15, 6/25, 8/25, 10/70, 12/70, 14/90, 16/90, 18/15, and 20/15 (T min/%B)). using mobile phase A as 10 mM ammonium formate buffer (pH 3.0) and mobile phase B as Ethanol with 0.5 mL/min as flow rate, 3 µL as injection volume and at 277 nm as UV wavelength. The PAN exhibited instability under solution state conditions characterized by acidic, basic, and oxidative conditions. The developed chromatographic method has been expanded to include QTOF-MS/MS to characterize the DPs in positive ionization mode. The developed HPLC method has undergone validation in compliance with the ICH guideline Q2 (R1). The method found linear from 12 µg/mL (LOQ) to 300 µg/mL with r2 ≥ 0.99. The specificity of the method was assessed through the peak purity of analyte and DPs. The% recovery for analyte was fall in the range of 99.28 to 100.36 with 0.60 % RSD. The%RSD for the analyte in Method precision and intermediate precision is below 1.0. The sample and standard solutions are stable upto 48 h at room temperature. The Green Analytical Principles (GAP) applied to the analytical method using GAPI, AGREE and Eco-Scale tools to assess the Greenness of the analytical method. The PAN and DPs were applied with ADMET prediction software indicated the carcinogenicity, mutagenicity for PAN and only carcinogenicity for DPs. The reproductive toxicity for shown for PAN, DP-2 and DP-3. The DP-3 has shown the penetration of the blood-brain barrier. The method is suitable for the quantification of PAN and its DPs as both active pharmaceutical ingredient and formulations in quality control and stability studies for its regular use

Combined green analytical principles and quality by design for ultraperformance liquid chromatography analytical method development, the characterization and in-silico toxicity prediction of Ixazomib degradation products using mass spectrometry

Ixazomib citrate (IC) is the first oral selective proteosome inhibitor for treating multiple myeloma. IC is prone to degradation due to its oxidative deboronation and the amide bond, affecting patient health, drug quality, and efficacy. The stability of IC is crucial during drug development as it guides the inherent stability of the molecule, its degradation pathways, packing materials, and formulation development. Following the International Conference on Harmonization (ICH) Q1A (R2) and Q1B, a stability study were performed for both solution and solid-state stress studies. Under oxidative and alkaline conditions, 3 degradation products (DPs) were identified, separated, and method-validated according to ICH Q2 (R1) guidelines. From the Design Expert statistical tool, the Central Composite Design was used to optimize the final analytical method conditions, where the p-values for the model are < 0.05%. Green analytical chemistry has significantly reduced the use of hazardous organic solvents without losing chromatographic performance. The green separation and quantification of DPs and IC on Ultra Performance Liquid Chromatography (UPLC) using an Inert-Sustain C8 (50×3.0) mm 2.0 µm column with gradient elution using 10 mM ammonium acetate buffer (pH 5.0) and ethanol at a flow rate of 0.5 mL/min and detection at 230 nm. The results of green assessment tools like GAPI, AGREE, and Analytical eco-scale found that the method is excellent for the greenness of utilizing ethanol as a solvent, shorter runtime, and lesser waste. The method was validated as per ICH Q2 guidelines, and the results found it is sensitive, precise, accurate, robust, and linear for its intended use. The method is suitable for quantifying IC and its DPs from 2.0 to 150 µg/mL with R2 values of 0.9996 with a detection limit of 1.0 µg/mL. The plausible degradation structures and pathways of DPs were outlined using tandem mass spectra employed on LC-QTOF-MS/MS in both ESI positive and negative modes. The mechanistic explanation for establishing DPs was explained in detail. The ADMET Predictor™ software predicted the physicochemical and ADMET properties. The toxicity profile reveals that DP2 and DP3 are teratogenic, while D1 and D3 show phospholipidosis