title: Structural elucidation of a new sildenafil analogue using high-resolution Orbitrap mass spectrometry.
abstract: BACKGROUND
  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 MS(2) 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 MS(2) 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.
authors.affiliation: Pharmaceutical Laboratory, Applied Sciences Group, Health Sciences Authority, 11 Outram Road, Singapore 160978. Kee_Chee_Leong@hsa.gov.sg
authors.forename: Chee-Leong
authors.initials: CL
authors.lastname: Kee
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ge
authors.forename: Min-Yong
authors.initials: MY
authors.lastname: Low
authors.forename: Hwee-Ling
authors.initials: HL
authors.lastname: Koh
mesh_terms: D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D015394:Molecular Structure; D008970:Molecular Weight; D010879:Piperazines / Q000737:chemistry*; D011687:Purines / Q000737:chemistry; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000737:chemistry*
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate