Determination of a new type of phosphodiesterase-5 inhibitor, thioquinapiperifil, in a dietary supplement promoted for sexual enhancement

Abstract

A new type of phosphodiesterase-5 (PDE-5) inhibitor, thioquinapiperifil (1), was found in dietary supplements. LC-MS analysis indicated that the supplements contain two major compounds. One was identified as thiodenafil (synonym: thiosildenafil) by direct comparison with the authentic compound. The other showed a molecular weight of 448, and accurate mass measurement showed its elemental composition to be C24H28N6O 1S1. Together, the mass and NMR spectrometric data revealed that the compound is an imidazoquinazoline derivative: 3-ethyl-l,3-dihydro-8-[[[2-[4-(hydroxymethyl)-l-piperidinyl]phenyl]methyl]amino] -2H-imidazo[4,5-g]quina-zoline-2-thione. This compound had been synthesized as a PDE-5 inhibitor, formerly reported as KF31327 by Kyowa Hakko Kogyo Co., Ltd. Considering this compound's general properties, it has been renamed thioquinapiperifil with the agreement of Kyowa Hakko Kogyo Co., Ltd. The detection of imidazoquinazoline-type compounds in dietary supplements has not been reported. Quantitative analysis showed that the contents of 1 and thiodenafil in the products were about 13 - 15 mg/tablet (43-48 μg/mg) and about 0.4 mg/tablet (1 μg/mg), respectively. © 2008 Pharmaceutical Society of Japan.