title: Determination of riociguat and its major human metabolite M-1 in human plasma by stable-isotope dilution LCMS/MS.
abstract: BACKGROUND
  Riociguat (BAY 63-2521) is an oral NO-independent as well as NO-synergistic stimulator of soluble guanylate cyclase (sGC) for the treatment of pulmonary hypertension. BAY 60-4552 (M-1) is its pharmacologically active major metabolite. An isotope dilution LC-ESI-MS/MS method has been developed and validated for the simultaneous determination of riociguat and M-1 in lithium heparinized human plasma.
  
  
  RESULTS
  The validated concentration range covers 0.500 μg/l (LLOQ) to 100 μg/l (ULOQ) for both analytes. Interassay accuracy and precision (%CV) for both analytes ranged from 92.7 to 111% and from 2.61 to 9.89%, respectively.
  
  
  CONCLUSIONS
  The method proved to be selective, specific, sufficiently sensitive, highly reproducible and robust for the analysis of large numbers of samples.
authors.affiliation: Drug Metabolism & Pharmacokinetics, Pharmaceutical Research Center, Bayer HealthCare AG, Aprather Weg 18A, D-42096 Wuppertal, Germany.
authors.forename: Mark-Jean
authors.initials: MJ
authors.lastname: Gnoth
authors.forename: Peter-Michael
authors.initials: PM
authors.lastname: Hopfe
authors.forename: Waldemar
authors.initials: W
authors.lastname: Czembor
mesh_terms: D001774:Blood Chemical Analysis / Q000379:methods*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D006801:Humans; D007553:Isotope Labeling; D011720:Pyrazoles / Q000097:blood* / Q000378:metabolism / Q000592:standards; D011743:Pyrimidines / Q000097:blood* / Q000378:metabolism / Q000592:standards; D011786:Quality Control; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards
chemical_list: C569640:BAY 60-4552; D011720:Pyrazoles; D011743:Pyrimidines; C542595:riociguat