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The following message was posted to: PharmPK
Hi everyone,
If I start working on a reported HPLC method and end
up modifying it drastically (for good resolution, lesser
cost, different matrix, detector
availability), does it become a new method or still a
modification of reported method??
Example
Reporteed method Modifications
pH 3.5 2.6
ion-pair octanesulfonicacid triethylamine
flow 0.8 ml 1.5 ml
Detection fluorescence UV
Sensitivity 10 uM 2 uM
matrix plasma plasma,RBC
separation isocratic gradient
extraction ACN:CHCl3 ACN:CHCl3
buffer 10mM KH2PO4 10mM KH2PO4
(UV is more sensitive in this case because at acidic
pH fluoroscence is quenched. Method is for
simultaneous analysis of three compounds and I get
baseline resolution and sharp peaks.)
Sunil Bajad,Ph.D.
Departmetn of Medical Sciences
UW-Madison,53706,USA
[Different detection/sensitivity could be considered a new method for
publication purposes and certainly for regulatory purposes - db]
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Sunil,
David is absolutely right, these are now different methods.
A very liberal list of "adjustments" that were proposed that could be
made to a method, without it becoming a new method, was published in
thePharmacopeial ForumVolume 25, Number 2, Mar. - Apr. 1999, pp. 7921 -
7927.
Sunil, the example provided exceeds even these liberal "adjustments",
e.g., pH change of +/- 0.2 units, change in detector wavelength of at
most +/- 3 nm.
Frank
Frank Bales, Ph.D.
Senior Regulatory Consultant
Worldwide Regulatory Affairs
PAREXEL Intl.
2520 Meridian Pkwy, Suite 200
Durham, NC 27713
Email: frank.bales.-at-.parexel.com
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Dear Bajad
Simply Yes!! whether you modify or not you have to validate.
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The following message was posted to: PharmPK
Dear Sunil,
To my knowledge, a full validation is required the first time an assay
is
implemented at a specific analytical site.
If, however, the reported method was already implemented at your site
in the
past and validated by means of a full validation, a partial validation
would
be sufficient to re-validate the assay changes.
Hope this helps.
Kind regards,
Bart Remmerie
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