Method development and validation

This system includes measures and activities related to laboratory procedures, testing, analytical methods development and validation or verification, and the stability program. 

Other features of an analytical method that should be borne in mind are its linear range, which should be as large as possible to allow samples containing a wide range of analyte concentrations to be analysed without further manipulation, and its precision and accuracy. Method development and validation require all of these parameters to be studied and assessed quantitatively. 

Berzas Nevado, J.J. et al.. Method development and validation for the simultaneous determination of dyes in food stuffs by capillary zone electrophoresis. Anal. Chim. Acta, 378, 63, 1999. 

M. Mulholland, N. Walker, J.A. van Leeuwen, L. Buydens, H. Hindriks and P.J. Schoenmakers, Expert systems for method development and validation in HPLC. Microchim. Acta, 2 (1991) 493-503. 

Another excellent example of the use for method development and validation appears in Morrison and Richardson (1996). Their laboratory was analyzing many samples of Li ore and related samples for Ba, among other elements, using a routine XRF procedure. The reference sample chosen as a control sample for the run was the zinnwaldite ZWC (Govindaraju et al. 1994), for which analyses produced a value approximately twice the reference value. Investigation of that result identified a Rb overlap in the X-ray spectrum that had not previously been observed in use of the method. 

Regulatory guidance and scientific consideration for residue analytical method development and validation... 

In summary, the proposal of an appropriate definition of the residue is not a process which follows simple and unambiguous rules in each case. The differences between residue definitions of some European MRLs and US tolerances illustrate the importance of harmonization. However, the great effort sometimes necessary to reach a suitable and accepted residue definition, which considers the needs of risk assessors (toxicologists) and the feasibility aspects of residue analysts, is clearly a vital prerequisite for any method development and validation. 

In any residue program, but particularly in an LSMBS, a well-established and validated method should be used. The alternative is to carry out method development and validation in parallel with the smdy, a course of action that is not recommended. 

H. Watzig, M. Degenhardt, and A. Kunkel, Strategies for capillary electrophoresis Method development and validation for pharmaceutical and biological applications, Electrophoresis, 19, 2695 (1998). 

Comparison of test values with a conventional true value ( reference value ) of a (certified) reference material (RM, CRM). In method development and validation of analytical procedures, the comparison of experimental results with standards of diverse kind (laboratory standards, certified reference materials, primary standards) plays an essential role. The decision as to whether an experimental result hits the reference value depends not only from the result itself but also from its uncertainty interval. 

Much of the methods development and validation efforts in the past have been focused on evaluation of immunosuppression and contact or dermal sensitization. Currently available animal models and assays are not valid to assess the potential for systemic hypersensitivity and, at this time, reliable models to assess autoimmunity are not available. 

Dr. Perry G. Wang is currently a principal scientist at Teleflex Medical. His interests include analytical method development and validation, medicated device products, and environmental engineering. His expertise focuses on high-throughput analysis of drugs and their metabolites in biological matrices with LC/MS/MS. 

Leeson LJ. ANDA dissolution method development and validation. Dissolution Technol 1997 4(1) 5—9, 18. 

The process of method development and validation covers all aspects of the analytical procedure and the best way to minimize method problems is to perform validation experiments during development. To perform validation studies, the approach should be viewed with the understanding that validation requirements are continually changing and vary widely, depending on the type of product under test and compliance with any necessary regulatory group. 

The first step in the method development and validation cycle should be to set minimum requirements, which are essentially acceptance specifications for the method. During method development, a complete list of criteria should be agreed on by the end users so that expectations are clear. Once the validation studies are complete, the method developers should be confident in the ability of the method to provide good quantitation in their own laboratories. The remaining studies should provide greater assurance that the method will work well in other laboratories, where different operators, instruments, and reagents are involved and where the method will be used over much longer periods of time. 

The primary object of this book is to provide the HPLC practitioner with a handy guide to the use of HPLC for analyzing pharmaceutical compounds of interest. This means familiarizing the practitioner with the theory, instrumentation, regulations, and numerous applications of HPLC. This handbook provides practical guidelines using case studies on sample preparation, column or instrument selection, and summaries of best practices in method development and validation, as well as tricks... 

A number of computer software packages are available to the analyst to assist in the planning and execution of both method development and validation experiments. The attraction of these systems is that they can automate the validation process from planning the experiment to test execution to the presentation of the data in a final report form. 

Other chromatographic systems snch as DryLab 2000 Pins from LC Resonrces (http //www.lcresources.com) incorporate aspects of method development and validation throngh simnlation software combined with actnal experiments to determine optimal operating conditions. This system is designed to generate efficient method development and method optimization experiments. Resnlts from these experiments can be nsed for the evaluation of robusmess as part of the validation for methods developed using this type of software. 

SokolieP, T., and Roller, G. (2005). Approach to method development and validation in capillary... 

Micke, G. A., Fujiya, N. M., Tonin, F. G., de Oliveira Costa, A. C., and Tavares, M. F. M. (2006). Method development and validation for isoflavones in soy germ pharmaceutical capsules using micellar electrokinetic chromatography. /. Pharm. Biomed. Anal. 41(5), 1625—1632. 

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