Photocyanine

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.

Photocyanine, a novel amphoteric phthalocyanine drug, showed favorable anticancer activity in vivo. Pharmacokinetic study in cancer patients is an important component in dose administration choice. In this study, a rapid, sensitive analytical method based on high-performance liquid chromatography with ultraviolet detection was developed and validated for the determination of four isomers of photocyanine (FD1-4) in cancer patients. Sample preparation involved liquid-liquid extraction with a combination of ultrasound and N,N-dimethyl formamide. Calibration curves (1/x(2)) offered satisfactory linearity for the four isomers of photocyanine. The lower limit of quantification (LLOQ) for FD1-3 isomers was 30 ng/mL, and LLOQ for FD-4 was 5 ng/mL. Inter- and intra-day accuracies for four isomers ranged from 96.6 to 105.5%, and 95.0 to 103.6%, respectively. Inter- and intra-day precision ranged from 4.8 to 8.9%, and 3.6 to 12.2%, respectively. Stability studies showed that photocyanine was stable. This method was successfully used to quantify photocyanine in a pharmacokinetic study in which a single-dose of photocyanine (0.1 mg/kg) was intravenously administered to patients with cancer. On the basis of the discovery that photocyanine has a half-life of 57.5 h in vivo, we suggest that avoiding light for a longer period is essential for patients undergoing photocyanine therapy.