Crystal structure and physicochemical properties of crystalline form of 2'-O-{3-[(7-chloro-4-quinolinyl)amino]propyl}-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A.

The intent of the study was to prepare and characterize crystalline form of 2'-O-{3-[(7-chloro-4-quinolinyl)amino]propyl}-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A (1), a novel 15-membered azalide derivative with antimalarial activity. The crystalline material was prepared by crystallization from acetonitrile reproducible in high yield and purity. Single crystal X-ray studies, X-ray powder diffractometry, differential scanning calorimetry, thermogravimetric analysis, moisture adsorption, Karl Fischer titration, gas chromatography, scanning electron microscopy, optical microscopy, solubility, and solid-state and solution stability were conducted to investigate physicochemical properties of the existing crystalline form.

A multi-technique approach using LC-NMR, LC-MS, semi-preparative HPLC, HR-NMR and HR-MS for the isolation and characterization of low-level unknown impurities in GW876008, a novel corticotropin-release factor 1 antagonist.

A multi-technique approach was applied in order to fully characterize four low-level unknown impurities of GW876008, a novel CRF(1) receptor antagonist. Liquid chromatography (LC)-NMR spectroscopy was used in combination with LC-MS to obtain detailed information regarding the structure of the two major impurities present in batches of GW876008 and observed in the first synthetic scale-up for preclinical use. Two additional impurities were unexpectedly found at greater levels in a large scale synthesis for clinical use and their structure was elucidated by means of high resolution (HR)-MS and HR-NMR, after a small scale preparative HPLC purification step.