Chemistry Reference
In-Depth Information
samples. The latter methods, while quantitative, are not usually concerned with low
concentrations of analyte, but only with the amount of the API in the drug prod-
uct. Because of the simplicity of the separation (the API must be resolved from all
interferences, but any other peaks in the chromatogram need not be resolved from
each other), emphasis is on speed over resolution. For assays in Category I, limit of
detection (LOD) and limit of quantitation (LOQ) evaluations are usually not neces-
sary because the major component or active ingredient to be measured is normally
present at high concentrations. However, because quantitative information is desired,
all the remaining analytical performance parameters are pertinent.
7.1.2 c
Ategory
II m
ethodS
Category II tests target the analysis of impurities or degradation products (among other
applications). An
impurity
test measures the minor components generally unintention-
ally in the substance or product, originating from the raw material manufacturing,
product manufacturing, or degradation during storage or processing. These assays
usually look at much lower analyte concentrations than Category I methods, and as
seen in Table 7.1 are divided into two subcategories: Quantitative and Limit Tests.
If quantitative information is desired, a determination of LOD is not necessary, but
the remaining parameters are required. The situation reverses itself for a Limit Test.
tAble 7.1
data elements required for general procedure validation (from usp
chapter 1225)
Analytical
performance
parameter
category II:
Impurities limit
tests
category I:
Assays
category III:
specific tests
category Iv:
I.d.
Quant.
tests
limit
tests
Accuracy
Ye s
Ye s
*
*
No
Precision
Ye s
Ye s
No
Ye s
No
Specificity
Ye s
Ye s
Ye s
*
Ye s
LOD
No
No
Ye s
*
No
LOQ
No
Ye s
No
*
No
Linearity
Ye s
Ye s
No
*
No
Range
Ye s
Ye s
No
*
No
Robustness
Ye s
Ye s
No
Ye s
No
Note:
Category I: Analytical procedures for quantitation of major components of bulk drug substances or
active ingredients (including preservatives) in finished pharmaceutical products. Category II:
Analytical procedures for determination of impurities in bulk drug substances or degradation com-
pounds in finished pharmaceutical products. These procedures include quantitative assays and
limit tests. Category III:
Analytical procedures for determination of performance characteristics.
Category IV: Identification tests. An asterisk indicates the parameter may be required, depending
on the nature of the test. For additional details, see Reference 5.
