Application of ion mobility spectrometry in analytical support of drug substance development

摘要

An investigation into the use of ion mobility spectrometry (IMS) for analytical support of drug substance development is reported. A group of thirty compounds including drug substances, starting materials and intermediates were analyzed by IMS, with 87% of the compounds affording a usable signal. The technique was further evaluated for single component quantification and multiple component quantification. A sub-ppm detection limit and a linearity range of 10 to 20 fold were obtained for most compounds tested, with the consecutive injection precision at less than 10% (RSD). Significant matrix effects on instrument response were observed when real reaction mixtures were analyzed. A spike/limit-testing method with a pre-established standard was developed for quick end of reaction monitoring. General advantages and limitations of the use of the IMS technique for drug substance development support are discussed, and some applications in areas such as starting material identification, high throughput screening and end of reaction monitoring are recommended.