Structural elucidation of a new sildenafil analogue using high-resolution Orbitrap mass spectrometry

RATIONALE One new phosphodiesterase type 5 (PDE‐V) inhibitor, propoxyphenyl homohydroxysildenafil (PP‐HHS), has been isolated from one health supplement, and analyzed using high‐resolution Orbitrap mass spectrometry. High‐resolution mass spectrometry (HRMS) is useful to elucidate unknown substances at low concentrations. METHODS Two isolated compounds, propoxyphenyl thiohomohydroxysildenafil (PP‐THHS) and propoxyphenyl homohydroxysildenafil (PP‐HHS), were infused into the Thermo Fischer Scientific LTQ Orbitrap XL™ hybrid FTMS system at a flow rate of 3 μL per min. The high‐resolution MS2 spectra were acquired using different high‐energy collision dissolution (HCD) mode; 40 V for PPT‐HHS and 45 V for PP‐HHS. The accurate mass measurement was assisted with the aid of Mass Frontier software, version 5.0. RESULTS The fragmentation pattern of PP‐HHS in the MS2 spectrum is very similar to that of PP‐THHS except the product ions at m/z 519, 501, 325, 299 and 283 are less than PP‐THHS by 16 m/z units. This is a result of the replacement of sulfur atom by oxygen at the thiolactam moiety. All the mass errors are below 5.0 ppm. CONCLUSIONS High‐resolution Orbitrap mass spectrometry is an alternative method to determine unknown compounds like PDE‐V inhibitor analogues unambiguously by analyzing the product ions at high mass accuracy. PP‐HHS is an unapproved drug and no pharmacological study has been reported. Hence, it could be harmful to unknowing consumers with undesirable side effects. Copyright © 2013 John Wiley & Sons, Ltd.