Method Equivalency

[cygg168]

When we tested the same lot of API and Drug product by UV (an usp method) and HPLC (an internally validated method), we had a trend that the HPLC gives consistantly higher results about 4-5% over the UV method. The sample preparation and UV wavelengths are different in the two methods. However, we use the same USP standard in both of the methods (not a salt or conversion factor etc), and in each method, the standard and the samples are prepared the same way and then the API and drug product were quantitated against the standard in that method. Can any one explain why the two methods give different results?

Most likely, the HPLC method is causing the problem because we got more than 100% for API result by the HPLC method. Still, we could not figure out what is causing the problem.

Any suggestions and comments are greatly appreciated.

[Don_Hilton]

With the many possibilities, my first reaction is to want to take a look at calibration data - for linearity, intercept, raw area as a function of concentration, analyte to internal standard area ratio. I would also want to look at chromatographic traces with integratin marks - blanks, calibration and all.