Separation of atropisomers by chiral liquid chromatography and thermodynamic analysis of separation mechanism.

In the pharmaceutical industry, the analysis of atropisomers is of considerable interest from a scientific and regulatory perspective. The compound of interest contains two stereogenic axes due to the hindered rotation around the single bonds connecting the aryl groups, which results in four potential configurational isomers (atropisomers). The separation of the four atropisomers is achieved on a derivatized β-cyclodextrin bonded stationary phase.

Ion-pairing HPLC methods to determine EDTA and DTPA in small molecule and biological pharmaceutical formulations.

Ion-pairing high-performance liquid chromatography-ultraviolet (HPLC-UV) methods were developed to determine two commonly used chelating agents, ethylenediaminetetraacetic acid (EDTA) in Abilify® (a small molecule drug with aripiprazole as the active pharmaceutical ingredient) oral solution and diethylenetriaminepentaacetic acid (DTPA) in Yervoy® (a monoclonal antibody drug with ipilimumab as the active pharmaceutical ingredient) intravenous formulation. Since the analytes, EDTA and DTPA, do not contain chromophores, transition metal ions (Cu, Fe) which generate highly stable metallocomplexes with the chelating agents were added into the sample preparation to enhance UV detection. The use of metallocomplexes with ion-pairing chromatography provides the ability to achieve the desired sensitivity and selectivity in the development of the method.

Drug interactions with potential rubber closure extractables. Identification of thiol-disulfide exchange reaction products of captopril and thiurams.

Mixtures of thiuram disulfides are frequently used as accelerators in rubber stoppers for injectables and sterilized powders for injection. Rapid reactions of thiuram disulfides between themselves and with thiols yield mixed disulfides due to thiol-disulfide exchange. The possibility of exchange reactions of thiuram disulfides extracted from rubber stoppers and drug products containing pendant thiol groups have not been reported in the analysis of potential stopper extractables.

Identification and control of a degradation product in Avapro film-coated tablet: low dose formulation.

A degradation product was formed during the long-term stability studies (LTSS) of the low dose formulation of Avapro film-coated tablet. The degradant was identified as the hydroxymethyl derivative (formaldehyde adduct) of the drug substance, irbesartan, based upon analysis with LC/MS, LC/MS/MS, and chromatographic comparison to the synthetic hydroxymethyl degradation product. Laboratory studies demonstrated that the interaction of individual excipients with the drug substance at elevated temperature and polyethylene glycol (PEG) used in the coating material, Opadry II White, leads to the generation of this formaldehyde adduct.