Abstract
Chlorin e6-C15-monomethyl ester (CMME) is a novel photosensitizer, which is synthetized from the degradation products of silkworm excrement. Preclinical studies on the promising photosensitizer CMME are necessary to determine its therapeutic efficacy and druglikeness. A high-performance liquid chromatography with UV detection (HPLC–UV) method was established for the determination of CMME in beagle dog plasma. The sample preparation involved a protein-precipitation method with acetonitrile after the addition of tanshinone IIA as an internal standard (IS). CMME and the IS were separated on a Diamonsil C18 (2) column (100 mm × 4.6 mm, 5 μm) with a isocratic system of methanol–water containing 20 mM ammonium acetate with 0.3% glacial acetic acid (85:15, v/v). The flow rate was 1.0 mL/min with UV detection using a wavelength of 400 nm. The method was sensitive enough with a lower limit of quantitation (LLOQ) of 0.05 μg/mL and had a good linearity (r2 > 0.999) over the linear range of 0.05–5.00 μg/mL. The intra-day and inter-day accuracies ranged from 98.5% to 102.8% and precisions (RSD) were within 6.8%. The validated method was successfully applied to the pharmacokinetic study of CMME after intravenous administration of single and multiple doses in beagle dogs.
Highlights
Photodynamic therapy (PDT) is a noninvasive method used for the treatment of malignant tumors based on the combination of the photosensitizer (PS) and light irradiation [1]
Chlorin e6, the most studied and best known photosensitizer used in PDT in many countries clear structure, betterpossesses tumor targeting ability,better strong photodynamic activity and lower cytotoxicity worldwide, clear structure, tumor targeting ability, strong photodynamic activity and lower cytotoxicity [3,10,11]. 2,7,12,18-Tetramethyl-3-ethenyl-8-ethyl-13-carboxyl-15-formyloxyethyl2,7,12,18-Tetramethyl-3-ethenyl-8-ethyl-13-carboxyl-15-formyloxyethyl-17-propionyloxy-17, 18-chlorin
Specificity of the method was investigated by blank plasma samples from six different sources, blank plasma spiked with internal standard (IS), blank plasma spiked with C15-monomethyl ester (CMME) at lower limit of quantitation (LLOQ) and plasma samples in a preclinical study
Summary
Photodynamic therapy (PDT) is a noninvasive method used for the treatment of malignant tumors based on the combination of the photosensitizer (PS) and light irradiation [1]. It can be used either as a primary or adjunctive treatment for solid cancers of various parts of the body including the bladder, esophagus, head and neck, brain, lung, prostate, intraperitoneal cavity, breast, prostate and skin [2]. Chlorin e6, the most studied and best known photosensitizer used in PDT in many countries clear structure, betterpossesses tumor targeting ability,better strong photodynamic activity and lower cytotoxicity [3,10,11]. PDT had gained more and more attention due to its significant advantages of destroying tumor cells effectively and selectively without injuring surrounding healthy tissues, and had been widely used as a new treatment that improves the quality of life of patients [2,3,4,5,6].
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