高效液相色谱验证-英文

28METHOD V ALIDATION FOR HPLC ANALYSIS OF RELATED SUBSTANCES

3.2BACKGROUND INFORMATION

3.2.1De nitions

De nitions for some of the commonly used terms in this chapter are given below.

Drug substance(active pharmaceutical ingredient):a pharmaceutical active ingredient.

Related substances:impurities derived from the drug substance and there-fore not including impurities from excipients.Related substances include degradation products,synthetic impurities of drug substance,and manufac-turing process impurities from the drug product.

Authentic sample:a puri ed and characterized sample of a related substance.

Unlike reference standards,authentic samples may not be of high purity.

However,the purity of an authentic sample has to be determined before use.Authentic samples are used in method development to identify related substances in the analysis.In addition,they are used extensively to prepare the spiked samples in method validation.

Spiked sample:a sample added with a known amount of related substances, prepared from authentic samples during method development or validation.

Control sample:a representative batch of drug substance(or drug product).

Typically,control samples are tested in all analyses to ensure consistency in method performance across different runs.Sometimes,they are used as part of the system suitability test to establish the run-to-run precision(e.g., intermediate precision,reproducibility).

Response factor:the response of drug substance or related substances per unit weight.Typically,the response factor of drug substance(or related substance)can be calculated by the following equation:

Response factor=response(in response units) concentration(in mg/mL)

Relative response factor:the ratio of the response factor of individual related substance to that of a drug substance to correct for differences in the response of related substances and that of the drug substance.It can be determined using the following equation:

Relative response factor=response factor of individual related substance response factor of drug substance

If a linearity curve(Figure3.1)is constructed for both the related substance and the drug substance by plotting the response versus the concentration, the relative response factor can also be determined by

Relative response factor=slope related substance slope drug substance