STRUCTURE OF CHEMICAL COMPOUNDS , METHODS OF ANALYSIS AND PROCESS CONTROL VALIDATION OF HPLC TECHNIQUES FOR PHARMACEUTICAL ANALYSIS

Validation (evaluation of suitability) of an analytical technique is a procedure aimed at obtaining experimentally justified evidence of the ability of this technique to give results characterized by the required accuracy and precision [1 – 7]. All analytical techniques used for the development of pharmaceuticals and for the determination of their quality characteristics have to be validated. In the case of using methods stipulated and described in the State Pharmacopoeia, it is not necessary to evaluate their suitability, provided that the analyses are conducted with strict observation of the text of each particular article. In most other cases, especially in cases of modification of the drug composition, the scheme of synthesis, or the analytical procedure, it is necessary to re-evaluate the suitability of the analytical techniques. This paper is aimed at (i) considering the peculiarities of validation of HPLC techniques for pharmaceutical analysis, (ii) critically assessing the main approaches to evaluation of the validation characteristics, and (iii) providing practical recommendations and criteria for finding correct solutions. The USSR State Pharmacopoeia (valid in the Russian Federation) introduced the section “Statistical Analysis of Biological Test Results” in 1968 (Xth Ed.) and the section “ Statistical Processing of Chemical Experimental Data” in 1988 (XIth Ed.). These sections are devoted to problems involved in the metrological attestation of analytical techniques. In 1987, the United States Food and Drug Administration (FDA) issued practical guides on the main principles of validation [5] and on the presentation of samples and analytical data pertaining to the validation of methods [6]. In 1993, the International Conference on Harmonization (ICH) developed generalized recommendations on the validation of analytical procedures; these documents were published in 1994 and treated in more detail in 1995 [1 – 3]. In 1994, the US FDA Center for Drug Evaluation and Research (CDER) issued a guide on the validation of chromatographic methods [4]. These documents and some review papers and monographs [9 – 13] provided a basis for extensive implementation of the procedure of validation of analytical methods. The Internet offers the Laboratory Guide to Method Validation and Related Topics at http://www.eurachem. ul.pt /. In recent years, new guides have become available from CDER [15], Waters Company [16], and Labcompliance [17 – 19]. Special sections are devoted to these problems in national and international pharmacopoeias and guides on the validation of analytical procedures [7, 20 – 22]. Also available are computer program packages, such as ELISA Method Validation Templates (Waters) and LaChrom 2000 Validation Manager (Merck) representing electronic tables with incorporated functions of statistical processing of the results of measurements and issuing validation certificates, and monographs on the related subjects [23 – 34]. Tables 1 and 2 summarize the most recent recommendations concerning selection of the validation characteristics depending on the type of analytical procedures. A comparative analysis of these data shows that, according to the United States Pharmacopoeia (USP-26), methods of dissolution testing have to be validated only with respect to precision (repeatability, reproducibility), while the other characteristics “may require validation, depending on the specific test nature. ” In contrast, according to the FDA CDER guidelines [15], procedures used for quantitative analysis and dissolution testing need the same validation characteristics. Pharmaceutical Chemistry Journal Vol. 38, No. 4, 2004