Utility of certain nucleophilic aromatic substitution reactions for the assay of pregabalin in capsules

<p>Abstract</p> <p>Background</p> <p>Pregabalin (PG) is an anticonvulsant, analgesic and anxiolytic drug. A survey of the literature reveals that all the reported spectrophotometric methods are either don't offer high sensitivity, need tedious extraction procedures, recommend the measurement of absorbance in the near UV region where interference most probably occurs and/or use non specific reagent that don't offer suitable linearity range.</p> <p>Results</p> <p>Two new sensitive and simple spectrophotometric methods were developed for determination of pregabalin (PG) in capsules. Method (I) is based on the reaction of PG with 1,2-naphthoquinone-4-sulphonate sodium (NQS), yielding an orange colored product that was measured at 473 nm. Method (II) is based on the reaction of the drug with 2,4-dinitrofluorobenzene (DNFB) producing a yellow product measured at 373 nm. The different experimental parameters affecting the development and stability of the reaction product in methods (I) and (II) were carefully studied and optimized. The absorbance-concentration plots were rectilinear over the concentration ranges of 2-25 and 0.5-8 μg mL^-1for methods (I) and (II) respectively. The lower detection limits (LOD) were 0.15 and 0.13 μg mL^-1and the lower quantitation limits (LOQ) were 0.46 and 0.4 μg mL^-1for methods (I) and (II) respectively.</p> <p>Conclusion</p> <p>The developed methods were successfully applied to the analysis of the drug in its commercial capsules. The mean percentage recoveries of PG in its capsule were 99.11 ± 0.98 and 100.11 ± 1.2 (n = 3). Statistical analysis of the results revealed good agreement with those given by the comparison method. Proposals of the reaction pathways were postulated.</p

Cyclooxygenase-2 inhibition delays the attainment of peak woven bone formation following four-point bending in the rat

Fracture healing is retarded in the presence of cyclooxygenase-2 (COX-2) inhibitors, demonstrating an important role of COX-2 in trauma-induced woven bone adaptation. The aim of this experiment was to determine the influence of COX-2 inhibition on the remodeling and consolidation of non-traumatic woven bone produced by mechanical loading. A periosteal woven bone callus was initiated in the right tibia of female Wistar rats following a single bout of four-point-bending, applied as a haversine wave for 300 cycles at a frequency of 2Hz and a magnitude of 65N. Daily injections of Vehicle (VEH: polyethyleneglycol) or the COX-2 inhibitor, DFU (2.0 mg.kg-1 and 0.02mg.kg-1 i.p.), commenced 7 days postloading, and tibiae were examined 2, 3, 4 and 5 weeks postloading. Tibiae were dissected, embedded in polymethylmethacrylate and sectioned for histomorphometric analysis of periosteal woven bone. No significant difference in peak woven bone area was observed between DFU-treated and VEH rats. But treatment with DFU resulted in a temporal defect in woven bone formation, where the achievement of peak woven bone area was delayed by one week. Woven bone remodeling was observed in DFU-treated rats at 21 days post-loading, demonstrating that remodeling of the periosteal callus is not prevented in the presence of a COX-2 inhibitor in the rat. We conclude that COX-2 inhibition does not significantly disrupt the mechanism of woven bone remodeling, but alters its timing