Back to the Top
Dear All,
We have developed and validated a method for simultaneous estimation
of four analytes (Fixed dose combination). Can the same validated
method be applied for the estimation of only two analytes of the above
combination present in the sample.
If partial validation required, what are the validation parameters to
be performed.
Thanks and regards
R.Gopinath
Back to the Top
Did you find any interaction between analytes such as inhibited or
enhanced
response when analytes were run separately compared with the
combination?
Improved or inhibited stability in matrix spike separately vs
combined? If
your validation did not show any negative or positive effects of the
combination on single drug parameters you may be okay.
On the other hand if you did not examine and or validate analytical
interactions you will need to do this. For example the efficiency of
ionization and or detection may be impacted (positively or negatively)
when
the combination of 4 is given vs a subset.
From a PK/PD standpoint your PKist will need to examine PK profiles to
determine what effect the combination of 4 has on PK vs the
combination of
2.
It is always simpler from a QA, bookkeeping, preparatory and analytical
standpoint to run 1 method/analyte. If you believe you get an
efficiency..
well.
I believe you would need to validate stability, (LLOQ and
ULOQ)linearity,
with accuracy and precision. Unless you have examined the drugs
independently as well as combined.
Edward F. O'Connor, PhD
78 Marbern Drive
Suffield, CT 06078
efoconnor.-at-.cox.net
Back to the Top
In my view you need to revalidate the method. U validated it for four
analytes that implies all the stabilities are performed in presence of
all the analytes and you dont know if any of the analyte is
contributing to the satbility of the others. Also the selectivity of
the method can be questioned. As the absence of two analytes can have
a considerable effect on the property of matrix used thereby producing
effect on extraction procedure. Also do remember, nowadays FDA is
emphasizing for incurred sample analysis which indicates that they
want the validation on the actual samples. So more you try to mimic ur
study samples more valid will be the method.
Dr. Mandar MoteSr. Manager Bio-analytical
Bio-equivalence Division
Macleods Pharmaceuticals Ltd.
Mumbai.
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "Bioanalytical method validation for FDC" as the subject | Support PharmPK by using the |
Copyright 1995-2011 David W. A. Bourne (david@boomer.org)