Development and validation of a high-resolution capillary electrophoresis method for multi-analysis of ragaglitazar and arginine in active pharmaceutical ingredients and low-dose tablets.
A selective, sensitive and robust capillary electrophoresis (CE) method has been developed and validated for multi analysis of ragaglitazar (also known as NNC 61-0029 or DRF 2725) and its counter ion arginine in Active Pharmaceutical Ingredients (API) and low-dose tablets (0.5, 1.0 and 2.0 mg). The method covers a total number of 12 analyses for the API and tablets: assay and identification of ragaglitazar and arginine, chiral purity of ragaglitazar and purity of ragaglitazar. After a simple extraction of samples with acetonitrile and 0.01 M sodium hydroxide (10:90), separation was performed using a combination of two cyclodextrins; sulfobutylether-beta-cyclodextrin (SB-beta-CD) and dimethyl-beta-cyclodextrin (DM-beta-CD) in the electrolyte. The method showed good specificity and could separate and detect ragaglitazar, the distomer (the (+)-enantiomer) and arginine. The LOQ was found to be 0.10%, corresponding to 0.2 ng (0.5 microg/ml) for ragaglitazar and the distomer. Linearity was observed to be from 0.5 to 15 microg/ml (range 0.2-60 ng) and 400-600 microg/ml (range 1603-2404 ng) for ragaglitazar and 166-250 microg/ml (range 668-1000 ng) for arginine. The accuracy (as percent recovery) for ragaglitazar was found to be 101-106% (at 400-600 microg/ml), 101-125% (at 0.5-15 microg/ml) and for arginine 97-101% (at 166-250 microg/ml). The repeatability for the detection of peaks as R.S.D. was found to be as follows, ragaglitazar: 0.05%, distomer: 1.01%, largest single impurity: 5.84%, total impurities: 0.90% and arginine: 2.00%. The intermediate precision for the detection of peaks as R.S.D. was found to be as follows, ragaglitazar: 0.63%, distomer: 1.98%, largest single impurity: 5.22%, total impurities: 13.17% and arginine: 3.50.
Jamali
Babak
B
Department of Analytical Development, CMC Development, R&D, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Maaloev, Denmark. bjam@novonordisk.com
Lehmann
Søren
S
D001120:Arginine / Q000032:analysis* / Q000737:chemistry; D019075:Electrophoresis, Capillary / Q000379:methods; D010078:Oxazines / Q000032:analysis* / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry; D010666:Phenylpropionates / Q000032:analysis* / Q000737:chemistry; D013607:Tablets
D010078:Oxazines; D004364:Pharmaceutical Preparations; D010666:Phenylpropionates; D013607:Tablets; D001120:Arginine; C432703:ragaglitazar