Determination of ragaglitazar, a novel dual acting peroxisome proliferator-activated receptor (PPAR) alpha and -gamma agonist, in human plasma by high-performance liquid chromatography coupled with tandem mass spectrometry.
A sensitive and specific LC/MS/MS method has been developed and validated for determination of ragaglitazar (NNC 61-0029 or DRF 2725) in human plasma. After solid-phase extraction (SPEC((R)) PLUS C(8)) of plasma, separation was performed on a Symmetry Shield RP8 column (mobile phase: acetonitrile: 10 mM ammonium acetate, pH 5.6 (40:60 v/v)). Two ranges were validated having LLOQs of either 0.500 or 100 ng/ml and linearity up to either 500 or 50000 ng/ml. The intra-assay precision and accuracy were 1.1% to 15.7% and 85.8% to 118.2% (range 0.500-500 ng/ml) and 2.0% to 8.8% and 92.9% to 104.8% (range 100-50000 ng/ml). The method was applied for determination of ragaglitazar in plasma from phase 1 and 2 clinical studies.
Andersen
Michael P
MP
Department of Pharmacokinetics, Research and Development, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Maaloev, Denmark. mipa@novonordisk.com
Nielsen
Karin K
KK
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D010078:Oxazines / Q000097:blood* / Q000494:pharmacology; D010666:Phenylpropionates / Q000097:blood* / Q000494:pharmacology; D010919:Placebos; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000819:agonists*
D010078:Oxazines; D010666:Phenylpropionates; D010919:Placebos; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C432703:ragaglitazar