File Entry: Route Evaluation and Analytical HPLC Method Development of Buprenorphine, Naloxone, and Comparison Overall Efficiency of Naltrexone Nalbuphine Traces the Evolution of Various Approaches

This is out line work on the process development for the synthesis of buprenorphine, naltrexone, naloxone, and nalbuphine from naturally occurring opiates such as Thebaine, also known as codeine methyl enol ether, and oripavine. Several new methods for N-demethylation of morphinans have been developed during the pursuit of this research. The article traces the evolution of various approaches and provides a comparison for overall efficiency. A reverse phase high performance liquid chromatographic (RPHPLC) method has been developed and validated for simultaneous estimation of Naloxone Hydrochloride and Buprenorphine Hydrochloride in pure and marketed formulations. Separation was carried out using column Hypersil ODS C18 (250 mm x 4.6mm x 5μm particle size) in isocratic mode using mobile phase composition pH 6.0 ammonium acetate Buffer: Acetonitrile (68:32)v/v and UV detection at 310nm. The compounds were eluted at a flow rate of 1.0mL/ min. The average retention times for Naloxone and Buprenorphine were 2.86 and 3.67 min, respectively. The method was validated according to the ICH guidelines. The percentage RSD of all validation parameters found to be less than 2% indicating high degree of accuracy and precision of the proposed HPLC method. The method was linear over the concentration of 5.30μg/ml and 20-120μg/ml for Naloxone and Buprenorphine respectively. The LOD and LOQ of Naloxone were found to be 0.08μg/mL and 0.26μg/mL and of Buprenorphine were found to be 0.0078μg/mL and 0.0237μg/mL. The drugs were also exposed to acidic, alkaline, oxidative, thermal and photolytic conditions and the stressed samples were analyzed by the proposed method. Degradation studies showed that the both the drugs were highly stable under acidic, oxidative, thermal and photolytic conditions. Under alkaline conditions, RT values were shifted to lower as compared to standard without any additional peaks. The high percentage of stability under stress conditions confirms the suitability of the method for simultaneous estimation of Naloxone Hydrochloride and Buprenorphine Hydrochloride in pure and marketed formulations.
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