Analytical Method Development and Validation

A stability indicating method must be developed and validated as early in the preformulation stage as possible. The Lrst few batches of a drug substance in the hands of preformulation scientists may be impure. The compound itself may be unstable, or it may be unstable in solvents used in solubility studies. Having an analytical method in place early on in the preformulation process is essential to ensure the quality of the preformulation results. 

For insoluble compounds, however, methods development is often complicated by solubility limitations. Typically, an organic solvent or some other solubilizing agents must be used for forced degradation studies and standards preparation. The effect of the solubilizing systems on the method should be considered as part of the methods development process. In addition, should the need for 

Will have solubility problems May have solubility problems No solubility problem 

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

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

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. 

Krull, I. S., and Swartz, M. (1999), Analytical method development and validation for the academic researcher, Anal. Lett., 32,1067-1080. 

Recently, major developments in statistical methods have been made particularly in the areas of collaborative studies and method validation and robustness testing. In addition, analytical method development and validation have assumed a new importance. However, this handbook is not intended to be a list of statistical procedures but rather a framework of approaches and an indication of where detailed statistical methods may be found. Whilst it is recognised that much of the information required is available in the scientific literature, it is scattered and not in a readily accessible format. In addition, many of the requirements are written in the language of the statistician and it was felt that a clear concise collation was needed which has been specifically written for the practising analytical chemist. This garnering of existing information is intended to provide an indication of current best practices in these areas. Where examples are given the intent is to illustrate important points of principle and best practice. 

Chauhan B, Rani S, Guttikar S et al (2005) Analytical method development and validation of mianserin hydrochloride and its metabolite in human plasma by LC-MS. J Chromatogr B Anal Technol Biomed Life Sci 823 69-74... 

Swartz ME, Krull IS. Analytical Method Development and Validation. New York Marcel Dekker, 1998 92. 

Swartz, M.E. Krull, I.D. Analytical Method Development and Validation Marcel Dekker, Inc. New York, 1997. 

II. Guidelines for analytical method development and validation of biotechnological synthesis of drugs. Production of a chiral steroid as model. 

The standard operating procedure (SOP) manual contains the procedures validated by the laboratory it is a complete set of instructions for pre-analytical, analytical and post-analytical methodology and also procedures for quality assurance/control, chain-of-custody and security. Each step in the handling of the specimen should be evaluated, optimized where possible and documented in the SOP. Important steps in the analytical process include collection, transport and accessioning of the specimen, sample preparation, isolation and detection of the analytes, production of the report and disposal of the specimen. This chapter focuses on the quality assurance and control issues for analytical method development and validation as well as statistical representation of the data. 

After Swartz and Krull [6]. Reprinted from M.E. Swartz et al., Analytical Method Development and Validation Marcel Dekfcer Inc., New... 

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