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We have been plagued by carry-over/contamination issues which we have
traced to our autosampler which is a part of a qualified LC-MS/MS
instrument system (high sensitivity triple quad). We decided to add
another autosampler option on the instrument, which required re-
qualification (IQ/OQ/PQ). For showing the suitability of the new
autosampler for the intended purpose (per regs), we chose to evaluate
the parameters of accuracy and precision through injections of an
aqueous standard into the mass spectrometer (analysis of peak area),
as well as a carry-over test. The qualification failed, with serious
concerns revealed about the accuracy and precision of the injections
the autosampler was making (%RSD between 10-20%), as well as some
carryover. When we informed the instrument manufacturer of the
inadequacies of the autosampler, they informed us that none of their
other clients have had problems qualifying the autosampler, and that
they were not aware of others testing these parameters when
requalifying a system.
Although it would not be fair to reveal the maker of the autosampler
without resolution of the problem, I assure you many of you are using
this instrument in your lab (has a very high reputation in the
industry).
Regarding our problem, I have a few questions:
1) in the example above, when such a change is made to a qualified
"system" what parameters are being requalified through OQ/PQ by other
laboratories in the regulated industry?
2) without great detail, how are these parameters tested? (eg.
Withdrawing liquid from weighed vial and reweighing? Injecting
standards and evaluating %recovery and %RSD?)
3) any good definitions for "for the intended purpose" for
requalification in this example (do you need to show satisfactory
results with MS detection if the purpose is to use the autosamp for
MS sample introduction)?
And finally:
4) any suggestions on how to minimize carryover on highly sensitive
MS platforms (Q-TOF, ABI 3000 4000 5000 or 4000QTrap, ThermoFinnigan,
etc.?)
Best regards,
Karen
Karen Veverka, Ph.D.
kveverka.at.gtxinc.com
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Hi Karen,
I suggest that by injecting in water, you are giving the analyte the
best chance of sticking to the autosampler. That results in both poor
reproducibility and carry-over. Try increasing the organic content
in the sample until it doesn't stick. You can usually find a mixture
that still allows a good separation - but not always!
How bad is the carry-over? 1% is not uncommon.
Regards.
Ted
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The following message was posted to: PharmPK
OOPS!
Sorry for the confusion: actually the compounds are dissolved in an
organic diluent (e.g. 40% acetonitrile). I used the term aqueous to
distinguish a non-plasma or other matrix based sample.
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