Structure elucidation of phototransformation products of unapproved analogs of the erectile dysfunction drug sildenafil in artificial freshwater with UPLC-Q Exactive-MS

J Mass Spectrom. 2014 Dec;49(12):1279-89. doi: 10.1002/jms.3461.

Abstract

In this study, four unapproved analogues of Sildenafil (SDF) were photodegraded under synthetic sunlight in artificial freshwater. Homosildenafil (H-SDF), hydroxyhomo-sildenafil (HH-SDF), norneosildenafil (NR-SDF) and thiosildenafil (T-SDF) were selected because they are frequently detected as adulterants in natural herbal products. Using UPLC-Orbitrap (Q Exactive)-MS, six photoproducts common to H-SDF, HH-SDF and T-SDF and nine unique transformation products of different molecular weights were identified based on their high-resolution (+)ESI product ion spectra. Mass spectral analysis of deuterated H-SDF, labeled on the N-ethyl group, allowed to gain mechanistic insight into the fragmentation pathway of the substituted piperazine ring and to support the postulated photoproduct structures. The mass spectral fragmentation confirmed the stepwise destruction of the piperazine ring eventually producing a sulfonic acid derivative (C17 H20 N4 O5 S: 392.1151 Da). In contrast, the photodegradation of NR-SDF, which lacks a piperazine ring in its structure, formed only two prominent photoproducts originating from N,N-dealkylation of the sulfonamide followed by hydrolysis. The current work constitutes the first study on the photodegradation of analogs of erectile dysfunction drugs and the first detection of two transformation products (m/z 449 and 489) in environmental samples.

Keywords: analogs of erectile dysfunction drugs; high-resolution mass spectrometry; photolysis; transformation products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Erectile Dysfunction / drug therapy
  • Fresh Water / analysis
  • Humans
  • Male
  • Photolysis*
  • Piperazine
  • Piperazines / analysis
  • Piperazines / chemistry*
  • Purines / analysis
  • Purines / chemistry
  • Pyrimidines / analysis
  • Pyrimidines / chemistry
  • Sildenafil Citrate
  • Spectrometry, Mass, Electrospray Ionization
  • Sulfonamides / analysis
  • Sulfonamides / chemistry*
  • Sulfones / analysis
  • Sulfones / chemistry
  • Sunlight
  • Tandem Mass Spectrometry
  • Vasodilator Agents / analysis
  • Vasodilator Agents / chemistry*
  • Waste Water / analysis
  • Water Pollutants, Chemical / analysis
  • Water Pollutants, Chemical / chemistry*

Substances

  • Piperazines
  • Purines
  • Pyrimidines
  • Sulfonamides
  • Sulfones
  • Vasodilator Agents
  • Waste Water
  • Water Pollutants, Chemical
  • Piperazine
  • Sildenafil Citrate
  • thiosildenafil