RP-HPLC Method Development and Validation for Cleaning Residue Determination of Tofacitinib Citrate in Tofacitinib Tablets

Abstract

A novel, Specific, and precise RP-HPLC method was developed to determine the residue content of Tofacitinib citrate left on the surface of equipment used in the manufacturing process. The manufacturing equipment considered in assessment of cleaning has been verified and found the tools assembled to the equipment are made up of Stainless steel, Glass, Teflon and plastic. Hence, these surfaces of manufacturing equipment that come in contact with the drug product during manufacturing are considered for evaluation of the cleaning procedure. By developing and validating an analytical method for residue estimation, the manufacturing equipment can be evaluated for efficient cleaning and to release the manufacturing equipment for further intended use by minimizing the cross contaminations. The stationary phase suited for the well separation of components is CAPCELL PAK C18 150 x 4.6 mm, 3 μm; 0.4 % perchloric acid and acetonitrile in the ratio of 85:15 % v/v is the mobile phase pumped at a flow rate of 1.2 mL/min through the column at temperature of 40 ºC. Each run extended for 10 min as the Tofacitinib peak elutes at RT of 5.2 min. The method has been validated successfully for Specificity, Precision, Linearity, Accuracy, Ruggedness and Filter validation of both rinse and swab methods. The LOD, LOQ concentrations found to be 0.006, 0.019 µg/mL for swab method and 0.03 and 0.1 µg/mL for rinse method respectively. The correlation coefficient is 0.999 and method found linear from LOQ to 500% for swab method and LOQ to 200% for rinse method. Solution stability has been established to ensure the test solution get tested within the stable time (4 Days). Based on the filter validation data, it is concluded that PVDF filter is not suitable for cleaning sample analysis and 2 mL sample should be discarded when 0.45 µm Nylon filter is used for cleaning sample analysis.