The Development Of Analytical Methods For Api Active Pharmaceutical Ingredient
Analytical methods play a role in the development of drugs, the role of the "lighthouse", is the development of raw materials and preparations, quality control of the ruler and the eye, so the api active pharmaceutical ingredient method in the drug development process played a role in the pilot. The following brief introduction to the development of raw material drug analysis method.
The development of analytical methods for raw materials is generally divided into two parts: First, the development of analytical methods for starting materials; Second, the development of analytical methods for intermediates and api active pharmaceutical ingredient. According to the normal logical order, it should be the starting material api active pharmaceutical ingredient method development first, but generally in the actual operation process, often the intermediate and api active pharmaceutical ingredient method first developed. Mainly because, in the process of opening up the process line or literature research stage, mainly for intermediate and API analysis of the work. Only in the middle of the process optimization or in the late, the initial material manufacturers will be selected when the basic start of the starting material analysis method development work. Even so, taking into account the logical sequence, or in accordance with the starting materials, intermediates, API this order to introduce one by one.
1, the starting material
Synthetic route acquisition
Before starting the analytical method development work, api active pharmaceutical ingredient it is necessary to obtain the synthetic route provided by the starting material manufacturer, including the following: starting materials, intermediates, reaction solvents, post-treatment solvents and key catalysts. If the manufacturers to provide reaction steps too long, generally choose 3-5 steps can be.
Impurity api active pharmaceutical ingredient
Combined with the starting materials manufacturers to provide the process line, may exist or produce a variety of impurities in a detailed api active pharmaceutical ingredient for the development of analytical methods to lay a foundation, but also the need for equipment in advance of the preparation.
The development of analytical methods
api active pharmaceutical ingredient The development of the corresponding analytical method is carried out according to the type of impurities involved in the starting material route. Based on the manufacturer COA and the analytical method provided, combined with the requirements of the starting material quality of the process, the internal control method for the starting material is established.
Verification of analytical methods
api active pharmaceutical ingredient Before the API process is carried out step by step, the pilot production batch is not less than 3 batches of pilot production batch samples, the use of a batch of analytical methods to verify the work of the remaining batches of analytical methods to reproduce the work, but also In order to verify the manufacturer to provide the stability and control of the starting material quality.
Determination of impurity limits
api active pharmaceutical ingredient According to the test results of multi-batch starting materials, as well as the requirements of API impurity limits, the limits of impurities in the starting materials are established in combination with the scavenging ability of the process route. Need to focus on genotoxic impurities and toxic reagents.