Spectrophotometric Quantitative Analysis of Aspirin and Vonoprazan Fumarate in Recently Approved Fixed-Dose Combination Tablets Using Ratio Spectra Manipulating Tools.

Background: Low-dose aspirin (ASP) is prescribed to millions of people around the world as a secondary preventative strategy for the majority of significant cardiovascular events; however, it carries a substantial risk of gastric ulcer and bleeding. Cabpirin® tablets, which include low-dose ASP and vonoprazan fumarate (VON), are approved in Japan for the treatment of acid-related diseases in patients who require a low dose of ASP but are at risk of ASP-associated gastric ulcers.

Objective: This paper describes the first published quantitative analytical approaches for the determination of ASP and VON.

Method: The normal ultraviolet absorption spectra of ASP and vonoprazan overlap significantly. The ratio spectra of the studied drugs were created and manipulated by ratio difference (RD) and first derivative of ratio spectra approaches. In the RD approach, the differences in the amplitude values between 229 and 283 nm enabled the quantitative analysis of ASP, and the differences in the amplitude values between 255 and 212 nm enabled the quantitative analysis of vonoprazan. In the first derivative of the ratio spectra approach, the created ratio spectra of each drug were transformed to the first-order derivative. ASP could be determined selectively at 237.40 nm without interference from vonoprazan. Moreover, vonoprazan could be determined selectively at 244 nm without interference from ASP.

Results: The applied approaches were validated according to the ICH guideline, with good results. Linear correlations were obtained for ASP and vonoprazan over concentration ranges of 2-25 and 1-10 µg/mL, respectively.

Conclusions: The described methods were optimized, validated, and applied for determination of the studied drugs in the synthetic mixtures and in pharmaceutical tablets without interferences.

Highlights: Two spectrophotometric ratio spectra manipulating approaches were developed for the determination of the ASP and vonoprazan in their pharmaceutical combination tablets.