Biomedical Engineering Reference
In-Depth Information
Table 1 Differences between CS/QC and incurred samples
CS/QC
Incurred Sample
Screening criteria for
matrix sources
Usually loose
Usually specific and strict dependent
on the objectives of a study, such
as age 40-50 and nonsmoker
No. of lots/sources
Usually more than one
source (pooled)
One single source
pH
Averaged due to pooling
More variable
Extra components
associated with
medication
None
Metabolite(s), comedication, and
nonactive ingredients in
formulation
Amount collected
Usually large, e.g., 200 mL
per collection
Usually small, e.g., 7 mL per
sampling time
No. of freeze-thaw cycles
prior to being extracted
Usually two or more
Usually one
Storage tube and preuse
storage
Usually stored at −20 °C and
without special protection
until being selected for a
speci fi c study
Could be collected under sodium
light and stored at −80 °C
immediately after collection
Amount of anticoagulant May be different because of different amounts collected
Note : CS Calibration standard, QC Quality control
Reproduced from ref. [ 36 ] with permission from Elsevier
criteria are necessary and need to be established a priori if incurred samples or ana-
lytical runs are rejected or repeated based on internal standard response variability.
In the authors' laboratory, the IS response of a sample is compared to the mean
IS response of the accepted calibration standards and quality controls in the same
run, i.e., those that meet the acceptance criterion of accuracy and do not show other
abnormality (e.g., poor chromatography). When the IS response of a sample is out-
side ±50 % of the mean IS signal of calibration standards and quality controls, the
sample will be repeated. Moreover, an investigation may be initiated for repeated
abnormal IS signal and when there is a pattern or trend. This acceptance criterion
was also recommended by others (e.g., [ 13 ]). Alternatively, though not reported,
some compare the IS response of a sample to those of adjacent samples or to the
mean IS response of all the samples in a batch. No matter what approach is used, it
is important to be able to single out abnormal samples and to perform corrective
actions to ensure that their reported concentrations are accurate.
3.3.3
Typical Causes of and Solutions to Internal Standard
Response Variations
Variation or Error in the Addition of Internal Standard
Apparently, any variation or error in the amount of the internal standard added to a
sample has a direct impact on IS response. Since the quantitation is based on ana-
lyte/IS response ratios, a prerequisite for good accuracy is that the same amount of
 
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