Chiroptical and vibrational spectroscopic study of genuine and counterfeit medicines containing tadalafil

• Published in: Chirality (New York, N.Y.) Vol. 30; no. 5; pp. 560 - 567
• Main Authors: Králík, František, Jirmásek, Patrik, Kuchař, Martin, Setnička, Vladimír
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-05-2018
• Subjects: ab initio calculations; Cialis; Circular dichroism; conformation; Counterfeit; Counterfeiting; Density functional theory; Dichroism; Erectile dysfunction; Infrared analysis; Infrared spectroscopy; Pharmaceuticals; Phosphodiesterase; Spectra; Spectrum analysis; structure; Tablets; Cialis; conformation; ab initio calculations; circular dichroism; structure
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.22828

The production and distribution of counterfeit pharmaceuticals present a serious problem worldwide. This is true especially in case of phosphodiesterase type 5 inhibitors for treating erectile dysfunction, where consumers often prefer buying them anonymously from unverified sources. In this study, genuine and counterfeit Cialis® 20 mg tablets were analyzed by electronic circular dichroism, vibrational circular dichroism, and infrared spectroscopy. The characteristic spectral patterns were identified by comparison with the spectra of tadalafil standard as an active pharmaceutical ingredient, and its presence was confirmed in all samples. The amount of tadalafil, however, was markedly lower in the case of counterfeit tablet as the observed band intensities were considerably lower. No other significant differences between the genuine and counterfeit tablets were revealed. Ab initio density functional theory calculations provided a detailed description of the stable conformers of tadalafil in a solution and enabled thorough interpretation of the experimental spectra.
This is the first study where electronic circular dichroism and vibrational circular dichroism spectroscopies were applied for an analysis of real Cialis® 20 mg tablets containing chiral tadalafil. The counterfeit was convincingly recognized from the genuine preparation as the amount of the active substance was significantly lower than that declared by the producer. Moreover, the 3D structure of tadalafil in a solution was described and the experimental spectra were subjected to a detailed interpretation based on density functional theory calculations.