Stability‐indicating method development and validation for quantitative estimation of assay and organic impurities of antiviral drug baloxavir marboxil in drug substance and pharmaceutical dosage form using HPLC and LC–MS methods

Abstract

Baloxavir marboxil (BXM) is a polymerase acidic endonuclease inhibitor used as an antiviral drug. A simple, reliable, and robust liquid chromatographic method was developed and validated per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2(R1) for estimating the assay and impurities of BXM in drug substance and pharmaceutical formulations. The chromatographic separation was carried out on C18 (100 × 4.6 mm, 5 μm) with binary solvent delivery system (A:0.1% trifluoroacetic acid in water; B:0.1% trifluoroacetic‐acid in acetonitrile) along with detection wavelength of 260 nm, column temperature of 57°C, flow of 1.2 mL/min and injection volume of 10 μL. All five known impurities and unknown impurities were separated well with resolution >1.7 and were estimated accurately without any interference. Recovered values and regression value were 99.5%–101.2% and R2 > 0.999, respectively. The recovery and linearity studies covered from 50% to 150% for assay, and quantitation limit, 120% for five BXM impurities. Stability‐indicating property of the HPLC developed method was assessed from the forced degradation studies. The mass spectral data of unknown impurity formed under oxidation stress condition were discussed. The developed method was also successfully utilized for stability sample analysis of drug substance and tablet dosage form.

Separation and quantitative estimation of stereo‐selective enantiomers of montelukast in pharmaceutical drug substance and tablets dosage forms by using stability‐indicating normal phase‐HPLC method

“…In the interest of optimizing the method, the experiments were conducted in a variety of trials utilizing various mobile phases, columns, and other chromatographic conditions 10–31 . The following is a summary of all the trials.…”

“…The stress testing discloses process‐related impurities, degradation‐related products, degradation pathways, and intrinsic stability 10–30 . The stability‐indicating characteristics of the proposed NP‐HPLC method was evaluated as follows using the stressed sample solution of 1.2 mg/mL.…”

“…As a result, the authors aimed to develop a new normal phase high‐performance liquid chromatography (NP‐HPLC) method for the separation and quantitative detection of the S‐enantiomer of montelukast in both pharmaceutical drug substance and drug products. The stability‐indicating characteristics of the developed NP‐HPLC method were proven through the stress testing studies, as all the peaks obtained from the placebo, solvents of the diluent or mobile phase, montelukast, and its other eight known impurities were separated well from each other without any interference 10–31 . The newly developed NP‐HPLC method was also capable of estimating the amount of the enantiomers of sulfoxide impurities (sulfoxide 1 impurity: R‐isomer, and sulfoxide 2 impurity: S‐isomer) in the MLS drug substance and formulated tablet dosage forms.…”

Stability‐indicating method for quantification of potential genotoxic impurity and other organic impurities of chlorzoxazone using hyphenated techniques

“…According to ICH, forced degradation experiments were conducted using chlorzoxazone active pharmaceutical ingredient (API), drug product, and placebo at test concentrations of 2.5 mg/mL to evaluate the degradation behavior of chlorzoxazone and respective excipients as well as the stability-indicating capabilities of the developed method [31][32][33][34]. The degradation study was conducted under different conditions, like photolytic (exposure light:…”

Stability‐indicating normal‐phase HPLC method development for separation and quantitative estimation of S‐enantiomer of lacosamide in pharmaceutical drug substance and tablet dosage form

“…for the separation and quantitative estimation of S-enantiomer of LA from both the drug substance and drug product (tablet dosage form). The stability-indicating properties of the developed test method were assessed using forced degradation studies (Bakshi & Singh, 2002;Blessy et al, 2014;Boppy et al, 2022;Carr & Wahlich, 1990;Ettaboina, Katakam, & Dongala, 2022;Ettaboina, Nakkala, & Chathalingath, 2022;ICH, 2003;Katakam, Ettaboina, & Dongala, 2021;Katakam, Ettaboina, & Marisetti, 2021;Lakka & Goswami, 2012;Lakka et al, 2021Lakka et al, , 2022Lakkireddy et al, 2015;Mohan et al, 2022;Nagulancha et al, 2023;Narasimha et al, 2011Narasimha et al, , 2020Narasimha et al, , 2022Siva et al, 2022;Snyder et al, 2010)…”