Analytical methods development and validation play essential roles in the discovery, development, and manufacturing of pharmaceuticals. Method development is the process of proving the acceptance of an analytical method for use to measure the concentration of an API in a certain compounded dosage form which allows simplified methods to be adapted to verify that an analysis procedure, precisely and consistently will deliver a reliable quantity of an active ingredient in a compounded preparation.
The analytical method development and validation is important for analytical method development and tested thoroughly for specificity, linearity, accuracy, precision, range, detection limit, quantitation limit, and robustness. On the whole, analytical method development and validation allows us to determine the accuracy and reliability potency measurement of a pharmaceutical preparation that can be performed.
The number of drugs introduced in the market is increasing every year. These drugs may either be new entities or partial structural modification of the already existing one. Often, there is a delay from the date of introduction of a drug into the market to the time of its inclusion in pharmacopeias.
This happens due to the possibility of uncertainties in the continuous and wider use of these drugs, reports of new toxicities which result in their withdrawal from the market,
development of patient resistance, and introduction of better and more reliable drugs by competitors. Under these conditions, standards and analytical processes for these drugs may not be available in the pharmacopeias. It becomes essential, therefore, to develop newer analytical methods for such drugs.
Analytical chemistry deals with methods for identifying, separating, and quantifying the chemical components of both natural and artificial materials. The choice of analytical methodology depends on many considerations, such as chemical properties of the analyte and its concentration sample matrix, the speed as well as the cost of the analysis, the number of samples, and type of measurements, i.e., quantitative or qualitative.
A qualitative method yields information about the chemical identity of the species in the sample. A quantitative method provides statistical information regarding the relative amounts of one or more of the analytes in the sample.
The steps of method development and method validation
are as follows.
- Method development plan definition
- Background information gathering
- Laboratory method development, it includes different stages namely sample preparation, specific analytical method, detection and data processing
- Generation of the test procedure
- A well-developed method must be easy to validate. A technique should be developed to rapidly test formulation prototypes, preclinical samples, and commercial samples. There are five general types of analytical methods, all with their own set of validation requirements
- Identification tests
- Potency assays
- Quantitative tests for impurities
- Limit test for the control of impurities
- Specific tests
The first four tests are universal tests that are performed by all analytical instruments manufacturers, but certain tests such as particle-size analysis and X-ray diffraction are used to control certain properties of the Active Pharmaceutical Ingredient (API) or the drug product.
The most widely used methods for quantitative determination of drugs and metabolites in biological matrices such as blood, serum, plasma, or urine includes High-performance liquid chromatography (HPLC), Gas chromatography (GC), Thin layer chromatography(TLC), combined GC and LC mass spectrometric (MS) procedures such as LC-MS, LC-MS-MS, GC-MS, and GC-MSMS, techniques like NMR is used for structure identification.