Application of isoindole fluorophore formation for determination of linagliptin in the sole and co-formulated tablets: Application for plasma assay and content uniformity testing

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Vol. 291; p. 122390
• Main Authors: Abu-hassan, Ahmed A., El Hamd, Mohamed A., El-Maghrabey, Mahmoud H., Mahdi, Wael A., Alshehri, Sultan, Shaaban Mohammed, Bassam
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 15-04-2023
• Subjects: Content uniformity; Diabetes Mellitus, Type 2 - drug therapy; Dipeptidyl-Peptidase IV Inhibitors; Fluorescent Dyes; Humans; Hypoglycemic Agents; Isoindole derivative; Linagliptin; Quality control and clinical studies; Spectrofluorimetric; Tablets; Isoindole derivative; Linagliptin; Quality control and clinical studies; Spectrofluorimetric; Content uniformity
• ISSN: 1386-1425; 1873-3557
• DOI: 10.1016/j.saa.2023.122390

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•The current approach describes an innovative method for linagliptin assay.•The assay is based on using o-phthalaldehyde as a fluorogenic probe to generate an isoindole fluorescent derivative.•The method was applied successfully for the dosage form, content uniformity, and plasma.•The method neglected strenuous steps such as extraction or heating.•The methods were validated and applied according to the instructions of ICH, FDA, and USP.
Linagliptin is a new medicament belonging to dipeptidyl peptidase-4 enzyme inhibitors group. The mentioned medication is used to cure type 2 diabetes and is taken orally as a monotherapy or in a co-formulation with metformin. or empagliflozin. Herein, a novel, straightforward, and cost-effective method for linagliptin assay was developed with a workable use of an isoindole derivative. The primary amine moiety present in linagliptin enables its condensation with o-phthalaldehyde to form a fluorescent product in the presence of a sulfhydryl group-containing compound (2-mercaptoethanol) 0.01 % V/V. The isoindole fluorophore yield was monitored at (λexcitation 337.8 nm, λemission 434.3 nm) and all experimental variables were meticulously checked and adjusted. Fluorescence intensity versus linagliptin concentration was plotted to construct the calibration graph, and excellent linearity was achieved at values between 50 and 2000 ng/mL. The validity of the method was verified through a rigorous examination of the ICH guidelines. The method application was successful for linagliptin in different dosage forms, content uniformity study, and monitoring in spiked plasma. The devised technique was demonstrated to be a promising, easy, and quick alternate method for linagliptin assayin clinical study and quality control.