Søren Lehmann | PubMed Health

PubMed2004

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.

Arginine↗

PubMed2004

Supplementing pharmaceutical analysis techniques using radiotracers.

Radiolabeled compounds can be used for alleviating the degradation pathways and mass balance of drug products in the solid formulation, because it provides a very sensitive and specific method of locating and measuring particular compounds. The present study utilizes this methodology on levormeloxifene-a partial oestrogen receptor agonist-in the solid dosage form. It demonstrates how radiotracers can be used as a supplement to conventional analytical methods to investigate the degradation pathways and mass balance of drug substances as well as how they can be useful to cross validate the traditional analytical methods developed for the determination of uniformity of content, assay, and purity. To decrease the study time, pilot studies-in which the product was stored at high pressures of molecular oxygen and elevated temperatures-were performed. Conditions mimicking the degradation processes taking place under standard storage conditions of the drug substance were found, and these super-enhanced stress conditions were applied. The study time was thereby dramatically decreased. The produced degradation products were studied by liquid chromatography with mass spectrometric detection. The most important degradation pathway was ascribed to the oxidation of the pyrrolidine nitrogen atom in levormeloxifene to an N-oxide derivative of the drug substance.

Drug Contamination↗