Abstract

AN OVERVIEW OF ANALYTICAL METHOD DEVELOPMENT APPROACHES FOR SPARSENTAN: A CRITICAL REVIEW OF UV SPECTROSCOPY, HPLC AND LC-MS TECHNIQUES

P. Ravi Kumar*, Periketi Ramya, Nikitha Sree, B. Sreelekha

Abstract

Sparsentan, marketed as Filspari®, is a first-in-class, orally active, single-molecule dual endothelin type-A (ETA) and angiotensin II type-1 (AT1) receptor antagonist (DEARA) that received United States FDA accelerated approval in February 2023, and full approval in September 2024, for slowing the decline of kidney function and reducing proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression. Chemically, it is 2-[4-[(2-butyl-4- oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2- (ethoxymethyl)phenyl]-N-(4,5-dimethylisoxazol-3- yl)benzenesulfonamide (C32H40N4O5S, molecular weight 588.76 g/mol), combining structural elements of the AT1- antagonist irbesartan with a biphenylsulfonamide ETAantagonist pharmacophore. As a recently approved new chemical entity, sparsentan currently lacks an extensive, officially compendial analytical database, making the systematic development of simple, sensitive, and stability- indicating analytical methods for its estimation in bulk drug, pharmaceutical dosage forms, and biological matrices an important and timely requirement for quality control, bioequivalence, and therapeutic drug monitoring purposes. This review consolidates the reported physicochemical and pharmacological profile of sparsentan and critically examines the applicability, principles, and comparative performance of the three analytical platforms most widely employed for small-molecule drug estimation – Ultraviolet (UV) spectrophotometry, High-Performance Liquid Chromatography (HPLC), and Liquid Chromatography-Mass Spectrometry (LC-MS/LC-MS/MS) – with respect to the structural features of sparsentan that govern its chromophoric behaviour, chromatographic retention, and ionisation characteristics. Representative, ICH Q2(R1)/Q2(R2)-aligned method-development strategies, validation parameters, and forced-degradation considerations are discussed and presented through comparative tables and schematic illustrations. The review concludes by highlighting the current scarcity of published, validated analytical methods specific to sparsentan and identifies this as an important direction for future analytical research in pharmaceutical quality assurance.

Keywords: Sparsentan; Filspari; IgA Nephropathy; Dual Endothelin Angiotensin Receptor Antagonist; UV Spectroscopy; HPLC; LC-MS/MS; Analytical Method Validation.