Development of a quantitative method for four photocyanine isomers using differential ion mobility and tandem mass spectrometry and its application in a preliminary pharmacokinetics investigation

Photodynamic therapy (PDT) has been accepted as an alternative treatment for cancer, and its target specificity can be achieved by controlling the location at which light activates the photosensitizer. Photocyanine, a novel anticancer phthalocyanine-based photosensitizer, is a mixture of 4 cis-isomers of a series of synthetic products, and accordingly, it is essential to verify whether there are differences in pharmacokinetics among the four isomers for clinical application, which requires reliable analytical methods to measure the plasma concentrations of the four isomers. An efficient LC-MS/MS method coupled with differential mobility spectrometry (DMS) for the simultaneous quantification of the four photocyanine isomers in human plasma was developed and validated herein. This method had a limit of quantification of 10 ng mL^-1 for each isomer and showed stable and reproducible inter- and intra-day results. Use of this method in preliminary pharmacokinetic studies in patients with esophageal cancer showed that the exposure and distribution of the four isomers were different, which had not been found in previous studies. The present research revealed that DMS was an effective tool for isomeric quantitation and that LC-DMS-MS/MS presented robust and reliable in biomatrix analysis. The method significantly improved peak separation and sensitivity compared with that of other LC-MS-based methods.