Typical IMS method validation parameters to be considered include selectivity, linearity, reproducibility, recovery and solution
stability. Selectivity of the analyte is determined based on evaluation of the molecular structure dictating the mode of detection.
Selectivity from the sample matrix is based on minimizing the interference from product excipients and cleaning detergents,
and should be examined before performing the recovery experiment. In addition, the linearity is based on a second-order polynomial
curve obtained from the response versus the amount introduced, as described previously. Reproducibility must be used to determine
the action level. Therefore, these parameters must be considered during method development and verified during validation.
Recovery. After determination of the action level, sample recovery is determined from a 10-in.2 stainless-steel coupon. A stock sample solution is prepared at 100% of the API concentration at the target level. The solution
is then spiked onto three separate stainless steel coupons. The surfaces are allowed to dry before swabbing with a clean Texwipe
alpha polyester swab. According to industry guidelines, the swabbing technique includes horizontal strokes to swab the entire
designated area with one side of the swab head and then vertical strokes with the other side of the swab head. Each swab is
then placed back into the vial containing sample diluent, extracted, and later analyzed for active content. Table I shows
the recovery values from stainless-steel surfaces and corresponding percent relative standard deviation (%RSD) at the action
level for a novel pharmaceutical compound under development.
Table I: Recovery of active from factory-finished, stainless-steel plates.
Table I shows the recovery results, which are typical of those generated by swabbing three different stainless-steel coupons.
The observed variation is primarily a result of the inherent variability in the surface finish of the coupon. These values
are independent of the analysis technique and may be optimized by adjusting the swabbing procedure and/or materials. However,
application of a predetermined correction factor to swab assay results can be used to compensate for recovery values as low
as 50% during method validation.
Solution stability. Sample and standard solution stability studies are typically performed to cover 24 h at room temperature. Additional validation
studies, such as robustness and intermediate precision, are not included in the authors' validation plan for a limit test.
All of the parameters described previously must meet pre-established criteria as defined in the validation protocol. The criteria
and validation protocol must conform to International Conference on Harmonization guidelines as well as internal standard
The ease of use and the small footprint of ion mobility spectrometry instrument allows for the system to be implemented in
various work environments, such as quality control, and to report results with great sensitivity (nanogram to picogram range).
Moreover, data reduction software package upgrade ensures 21 CFR Part 11 compliance. The use of this software, in addition to a limit test, has simplified the process of data manipulation,
resulting in high-confidence passes for each clean sample analyzed.
Elizabeth Galella* is a research scientist, Scott Jennings is a senior research scientist, Madhavi Srikoti is an associate research scientist, Elizabeth Bonasso is a research scientist, all at the analytical research and development unit of the Pharmaceutical Research Institute, Bristol-Myers
Squibb, One Squibb Drive, New Brunswick, NJ 08903, firstname.lastname@example.org
*To whom all correspondence should be addressed.Submitted: Oct. 20, 2008. Accepted: Dec. 30, 2008.
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