Methods for validating requirements


Also, according to these regulations [21 CFR 211.194(a)(2)], users of analytical methods described in the USP and the NF are not required to validate accuracy and reliability of these methods, but merely verify their suitability under actual conditions of use.Recognizing the legal status of USP and NF standards, it is essential, therefore, that proposals for adoption of new or revised compendial analytical methods be supported by sufficient laboratory data to document their validity.According to Section 501 of the Federal Food, Drug, and Cosmetic Act, assays and specifications in monographs of the United States Pharmacopeia and the National Formulary constitute legal standards.The Current Good Manufacturing Practice regulations [21 CFR 211.194(a)] require that test methods, which are used for assessing compliance of pharmaceutical products with established specifications, must meet proper standards of accuracy and reliability.However, in most cases a submission will consist of the following sections.This section should identify the need for the method and describe the capability of the specific method proposed and why it is preferred over other types of determinations.For preparative HPLC, refractive index is preferred because it can handle high concentrations without overloading the detector.should be used, which detects all sample components that contain chromophores. The excitation wavelength locates the excitation maximum; that is, the wavelength that gives the maximum emission intensity.



A flow rate of 1-1.5 m L/min should be used initially. Fluorescence or electrochemical detectors should be used for trace analysis.The method can also be used for samples containing analytes with a wide range of retentivities that would, under isocratic conditions, provide chromatograms with capacity factors outside of the normally acceptable range of 0.5–15.Gradient HPLC will also give greater sensitivity, particularly for analytes with longer retention times, because of the more constant peak width (for a given peak area, peak height is inversely proportional to peak width).For example, a satisfactory separation may be found during step 2, thus steps 3 and 4 may not be required.