Chemistry Reference
In-Depth Information
standard is very important. The FDA recognizes two categories of reference standards:
compendial and noncompendial. Compendial reference standards are obtained from
sources such as the USP and do not need further characterization. Noncompendial
reference standards are standards of the highest purity that can be obtained by reason-
able effort and should be thoroughly characterized to assure its identity, strength, and
purity. It is generally recognized that more rigorous tests are often used to define the
reference standard than those used to define the drug substance itself. It is also recom-
mended that purity correction factors be included in any method calculations, along
with any other correction factors that may be applicable (e.g., moisture).
5.8
system suItAbIlIty protocol
System suitability must be performed on a regular basis. However, in spite of this
requirement, a review of common method deficiencies on the FDA Internet website
indicates that system suitability tests are not always routinely performed. On any
given day that unknown samples are to be run, it is customary to perform a sys-
tem suitability test analyzing unknown samples. Unless otherwise specified in the
method or USP monograph, data from five replicate injections are used to calculate
the relative standard deviation (RSD) if the requirement is 2.0% or less; data from six
replicate injections is used if the RSD requirement is more than 2.0%.
All data should be identical, within experimental error, and if the specifications
are not satisfied, then any subsequent quantitative results are suspect. Table 5.5 lists
some example system suitability specifications that have been used in the authors'
laboratory. Table 5.6 illustrates an example sample queue that utilizes a system suit-
ability test. If the system suitability specifications are met during the execution of the
sample queue, the entire sample queue is completed. However, if the specifications
are not met, an out-of-specification (OOS) result is generated (Chapter 6), an inves-
tigation is launched, and no unknown samples are analyzed until the investigation
is complete, the fault resulting in the OOS is corrected, and subsequent system suit-
ability tests are successful.
tAble 5.5
example system suitability specifications
parameter
Acceptance criteria
System Suitability
Linearity
r
2
≥ 0.99
Resolution between analyte of interest and next peak
≥2.5
Retention time of analyte
8.0 ± 1 min
Overall standard precision (5 injections)
Area RSD ≤ 2%
Retention time RSD ≤ 1%
Efficiency (plates)
N > 7500
Tailing factor
t
f
≤ 1.5
S/N of low-level analyte peak (e.g., LOQ level)
S/N ≥ 10
Check std. recovery
98% to 102%
