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Vol. 38 No. 5 (2026): Vol 38, Issue 5, 2026

Copyright (c) 2026 Shrikant Kulkarni, Sharad Panchgalle, Santosh Deosarkar, Vijaykumar More

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Advanced LC-MS/HRMS Strategies and Relative Response Factor Approaches for Impurity Profiling of Asthma Inhalation Drugs: A Critical Review

https://doi.org/10.14233/ajchem.2026.35730
Shrikant V. Kulkarni
Sava Healthcare Limited, Research Centre, Block D1, Plot No. 17/6, MIDC, Chinchwad, Pune-411019, India
https://orcid.org/0000-0002-1842-0826
Sharad P. Panchgalle
Department of Chemistry, K.M.C. College Khopoli-410203, India
https://orcid.org/0000-0001-9706-7567
Santosh D. Deosarkar
School of Chemical Sciences, Swami Ramanand Teerth Marathwada University, Nanded-431606, India
https://orcid.org/0000-0002-3056-9092
Vijaykumar S. More
Department of Chemistry, Kai. Rasika Mahavidyalaya, Deoni-413519, India
https://orcid.org/0000-0002-6110-8774

Corresponding Author(s) : Vijaykumar S. More

vijaymore@gmail.com

Asian Journal of Chemistry, Vol. 38 No. 5 (2026): Vol 38, Issue 5, 2026

Abstract

Asthma inhalation drug products deliver low doses directly to the lungs, demanding stringent control of impurities and degradation products. The chemical diversity of inhaled corticosteroids (ICS), β2-agonists (SABA/LABA) and muscarinic antagonists (LAMA), together with complex formulation/device systems (DPI, MDI, nebulizers), creates analytical challenges not fully addressed by general impurity profiling strategies. This review critically examines advanced LC-MS/HRMS strategies and relative response factor (RRF) approaches for impurity profiling and quantitation of asthma inhalation drugs and drug products, with emphasis on forced degradation design, inhalation-specific impurity risks and trace-level quantitation when impurity standards are unavailable. Literature on forced degradation, LC-MS/HRMS impurity identification, stability-indicating method development and RRF estimation for asthma inhalation APIs and combinations was assessed. Representative workflows and case studies were extracted, compared and synthesised to provide practical guidance for analytical development and quality control. HRMS-based workflows (QTOF and Orbitrap) enable high-confidence structural elucidation of unknown degradants, including oxidation, hydrolysis, photolysis and rearrangement products. Inhalation-specific risks include propellant/excipient interactions, humidity-driven solid-state transformations, extractables/leachables and container-closure induced degradation. RRF approaches using UV, CAD/ELS, CLND, NMR and MS-based normalisation strategies support impurity quantitation in the absence of reference standards, but require careful validation and uncertainty management. A targeted impurity profiling strategy for asthma inhalation products should integrate inhalation-relevant forced degradation design with orthogonal analytical workflows, including LC-MS/HRMS for identification and robust RRF-based quantitation frameworks. Future improvements are expected from predictive response modelling, standard-free quantitation and systematic integration of device formulation API degradation knowledge into analytical lifecycle management.

Keywords

Asthma inhalation Impurity profiling Forced degradation LC-MS HRMS Relative response factor
(1)
Kulkarni, S. V.; Panchgalle, S. P.; Deosarkar, S. D.; More, V. S. Advanced LC-MS HRMS Strategies and Relative Response Factor Approaches for Impurity Profiling of Asthma Inhalation Drugs: A Critical Review. ajc 2026, 38, 1105-1116.
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Author Biographies

Sharad P. Panchgalle, Department of Chemistry, K.M.C. College Khopoli-410203, India

Department of Chemistry, K. M. C. College Khopoli, 410203, Dist. Raigad, (M.S.), India

Santosh D. Deosarkar, School of Chemical Sciences, Swami Ramanand Teerth Marathwada University, Nanded-431606, India

School of Chemical sciences, Swami Ramanand Teerth Marathwada Univrsity, Nanded India- 431606

Vijaykumar S. More, Department of Chemistry, Kai. Rasika Mahavidyalaya, Deoni-413519, India

Department of Chemistry, Kai. Rasika Mahavidyalaya Deoni, Dist.- Latur, (M.S.), India-413519

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