ABSTRACT
Diabetic foot ulcer (DFU), if untreated, accounts for lower-limb amputations affecting patients' quality-of-life. Diperoxochloric acid (DPOCL) is known to heal DFU by its antibacterial and fibroblast stimulating activity. This was a phase 3, multicentre, randomized, double-blind, active-controlled, parallel-group study conducted to evaluate the efficacy and safety of topic solution of DPOCL compared with isotonic sodium chloride solution (ISCL). Adult patients with type 1 or 2 diabetes with random blood glucose levels of <250â mg/dL, with ≤ than three full-thickness foot ulcers were enrolled. Primary efficacy endpoint was complete wound closure and secondary was wound surface area. Adverse events were analyzed as safety endpoint. Of 311 enrolled patients, 289 were randomized 1:1 to DPOCL (139) and ISCL (150) treatment (10-weeks [8-Visits]). Percentage of patients with complete wound closure at visit-8, were significantly higher (P = .0156) in DPOCL arm (76% [105/139]) compared to ISCL (62% [93/150]) arm. At end-of-study, mean wound surface area in DPOCL arm (0.639â cm2) was significantly lower (P = .0209) compared to ISCL (0.818â cm2) arm. One death was reported in control arm which was not considered as treatment-related. No important safety finding were observed. Results indicate that, DPOCL can be considered as effective and safe treatment option for DFU compared to ISCL, although future confirmatory studies are warranted.
ABSTRACT
A rapid and sensitive liquid chromatography tandem mass spectrometry method has been developed and validated for the determination of the active metabolite (R-138727) of prasugrel in human plasma. Because R-138727 contains a thiol group, it requires stabilization by derivatizing with N-ethyl maleimide. Commercially available trandolapril was used as the internal standard (IS). The derivatives of R-138727 and IS were extracted from human plasma using a liquid-liquid extraction technique. Chromatography was performed on a Hypurity C18, 5 µ (50 mm × 4.6 mm, i.d.) column, with the mobile phase consisting of acetonitrile and 10 mM ammonium formate (pH 3.0, 50:50 V/V), followed by detection using mass spectrometry. No significant endogenous peaks corresponding to R-138727 or IS were detected in the blank human plasma samples and no significant matrix effect was observed for R-138727 and IS in the human plasma samples. The mean recovery for R-138727 ranged from 90.1 to 104.1%, with the lower limit of quantification set at 1 ng/ml. Linearity was established for concentrations in the range of 1.0-500.12 ng/ml, with a coefficient of determination (r(2) ) of 0.9958. The derivatized R-138727 was stable in human plasma for 3 months at -20 °C. This method increased the sensitivity and selectivity, resulting in high-throughput analysis of R-138727 using trandolapril as the IS in pharmacokinetic and bioequivalence studies, with a chromatographic run time of 3.7 min.
