Development of a UPLC-MS/MS method for the quantification of sildenafil by DBS, and its use on pediatric pulmonary hypertension

Bioanalysis. 2014;6(21):2815-24. doi: 10.4155/bio.14.126.

Abstract

Background: Sildenafil is used for the treatment of pediatric pulmonary hypertension. A dried blood spot (DBS)-based LC-MS method for sildenafil quantitation was developed and applied to a group of patients.

Results: DBS showed high portability and stability of samples, and the method was selective and linear for quantitation of sildenafil (5-3,000 ng/ml) and N-desmethyl-sildenafil (3-1,500 ng/ml). After a single oral dose of sildenafil (1 mg/kg), method evidenced poor metabolism in these patients.

Conclusion: The method was successfully applied in peripheral blood and can be used for both pharmacokinetics and therapeutic drug monitoring. DBS proved to have advantages during sample translation and preservation of analytes. Data suggest that hazardous blood sildenafil levels may be reached in this population.

MeSH terms

  • Child
  • Child, Preschool
  • Chromatography, High Pressure Liquid*
  • Dried Blood Spot Testing
  • Drug Monitoring
  • Female
  • Half-Life
  • Humans
  • Hypertension, Pulmonary / drug therapy
  • Male
  • Piperazines / blood*
  • Piperazines / pharmacokinetics
  • Piperazines / therapeutic use
  • Purines / blood
  • Purines / pharmacokinetics
  • Purines / therapeutic use
  • Sildenafil Citrate
  • Sulfonamides / blood*
  • Sulfonamides / pharmacokinetics
  • Sulfonamides / therapeutic use
  • Tandem Mass Spectrometry*
  • Vasodilator Agents / blood*
  • Vasodilator Agents / pharmacokinetics
  • Vasodilator Agents / therapeutic use

Substances

  • Piperazines
  • Purines
  • Sulfonamides
  • Vasodilator Agents
  • Sildenafil Citrate