Chemistry Reference
In-Depth Information
tAble 5.4
system suitability parameters and recommendations
parameter
recommendation
The peak should be well resolved from other peaks and the void volume,
generally k′ > 2.0
Capacity Factor (k′)
Repeatability
RSD ≤ 1% for N ≥ 5 is desirable
Relative Retention
Not essential as long as the resolution is stated
Resolution (R
s
)
R
s
> 2 between the peak of interest and the closest eluting potential interferent
(impurity, excipient, degradation product, internal standard, etc.)
Tailing Factor (T)
T ≤ 2
Theoretical Plates (N)
In general, should be > 2000
Source:
Center for Drug Evaluation and Research (CDER), Reviewer Guidance: Validation of
Chromatographic Methods, US Government Printing Office, 1994, 615-023-1302/02757.
5.7 system suItAbIlIty stAndArds
The USP defines a system suitability standard as a sample that consists of a mixture
of main components and any additional materials used in the control of the analytical
system [17]. The system suitability standard is distinctly different from other samples
or standards often used in the method development and validation process, such as
quality control samples, or standards and samples used for calibration or quantitation.
At times, the use of the pure analyte of interest standard alone without any sample
components present (e.g., blood, formulations, urine, etc.) is justified, for example,
during method development and optimization. However, this type of sample should
not be considered appropriate for system suitability because it contains but a single
component (the standard of the analyte). True system suitability standards are usu-
ally a little more complex than analyte quantitation standards because they usually
contain several of the expected, major components of the final sample (analyte plus
[perhaps]) impurities, metabolites, or degradants).
Quantitation and calibration standards often only contain one major component
and as such are not necessarily appropriate for system suitability determinations.
System suitability samples must contain at least the major analyte of interest and
ideally a closely eluting component or components that might be found in actual
unknown samples, at known levels. These other components could be synthetic pre-
cursors normally found in the preparation of the analyte itself, thermal or photo-
stability (breakdown) products, metabolites, or impurities. Thus, to prepare a useful
system suitability standard, a pure sample of the analyte standard (bulk drug) and
at least one of the expected, other major components in the HPLC chromatogram
should be used, because it is necessary to have more than one component present in
the sample in order to document the parameters called out in the USP [17].
System suitability standards, such as quantitation or calibration standards, are usu-
ally prepared from reference standards. Chromatographic methods rely heavily on
reference standards to provide accurate data. Therefore, the purity of the reference
