Abstract

METHOD DEVELOPMENT AND VALIDATION OF CLEANING PROCEDURE FOR THE RESIDUAL DETERMINATION OF 2-NITRO-5-PHENYLSULFANYL-PHENYLAMINE IN BULK DRUG MANUFACTURING BY REVERSE PHASE HIGH PRESSURE LIQUID CHROMATOGRAPHY

N. H. Eswara Prasad, D. Rama Devi, Dr. B. M. Rao, N. V. N. B. Srinivasa Rao, Y. V. Sunil Kumar and Dr. K. Basavaiah*

ABSTRACT

The objective of Cleaning Validation is to establish cleaning procedures and residue limits that are practical, achievable and verifiable and assure safety. Cleaning of the equipment train, utensil and / or components are carried out separately or clubbed followed by visual verification and testing. The purpose is to establish documented evidence to assure that, cleaning procedure and methods can repeatedly and reproducibly remove residue of the subjected product within the established acceptance limit. The acceptance limit is maximum allowable quantity of product residue, which does not affect quality and safety of the subsequent product to be manufactured, by using same equipment and facility. During development of cleaning validation importance should be paid to the residue and contaminants. The residue and contaminants shall include the absence of previously manufactured product, equipment related materials such as equipment linings, gaskets, filter agents and / or lubricants. Recovery shall be established using the swab technique and rinse technique and shall be within the acceptable limit. The main study depicts the development and validation of a RP-HPLC Cleaning method for the residual determination of 2-Nitro-5-phenylsulfanyl-phenylamine in veterinary active pharmaceutical ingredient manufacturing. The method was developed by using the isocratic solvent system, methanol and HPLC grade water in the ratio of 75:25 (v/v) and water is used as diluent. Successful elution of the 2-Nitro-5-phenylsulfanyl-phenylamine was achieved on Hypersil ODS with 250 x 4.6 mm and 10μm particle size. The method validation was successfully applied for routine analysis for cleaning/residual samples. The developed RP-HPLC method was validated with respect to system suitability, specificity, linearity, limit of quantitation, limit of detection and recovery study (rinse recovery and swab recovery).

Keywords: 2-Nitro-5-phenylsulfanyl-phenylamine, Reverse phase high performance liquid chromatographic (RPHPLC), Validation and residual determination.