Back to the Top
The following message was posted to: PharmPK
Dear all,
I am working with a CRO's bioanalytical department. My question is
how to
select LLOQ point in the calibration curve.Is any relation with Cmax?
We are
selecting this point as the lowest quantifiable point with the
acceptable
limit of accuracy and precision and cover the all the time point.
And also let me know the role of 1/X, 1/X^2 weighting factor.
Regards
Saji
Back to the Top
The following message was posted to: PharmPK
Dear all,
I am working with a CRO's bioanalytical department. My question is
how to
select LLOQ point in the calibration curve.Is any relation with Cmax?
We are
selecting this point as the lowest quantifiable point with the
acceptable
limit of accuracy and precision and cover the all the time point.
And also let me know the role of 1/X, 1/X^2 weighting factor.
Regards
Saji
Back to the Top
Dear Saji,
There is two visions to this dilemma (i.e. a pharmacokineticist and
an analytical one).
The pharmacokineticist will want a LOQ as low as possible in order to
calculate the elimination rate as far as possible.
The analytical problem with this is the dynamic range of your
detector. The FDA guidelines on bioanalytical method suggest to use
the simplest regression model possible (i.e. linear or weighted linear)
Thus, there is no simple answers to your question. In practice, we
try to establish the possible Cmax and divide in by 32 or 64 which
would result in 4 to 5 half-lives.
Hope this information is helpful.
Regards,
Sylvain Mandeville, Ph.D.
LAB Research Inc.
sylvain.mandeville.-a-.labinc.hu
Back to the Top
Hello,
It is usually done by Cmax/32 of course you should check the dose the
cmax is
referring to. Some people refer to literature to substantiate their
choice
of LLOQ.
Choice of weighting is for the purpose of improving the linear
relation ship
in your curve where the normal equation does not prove to be linear.
This is the best I can explain it
Regards,
Raja Sammour
QA Supervisor
Triumpharma
Back to the Top
The following message was posted to: PharmPK
The bottom line of the culibration curve is that it should be in a
position to detect even the smallest concentration of drug(active
principle) released. For instance during dissolution test sometimes a
very small amount of drug is released until the Formula used in the
formulation is improved.
Even in pharmacokinetics sometimes very small amount of drug
ultimately reach the blood.
The method developed should be in a position to detect all these.
s.o.o
Back to the Top
Dear Mr. Saji,
You can calculate the LLOQ Point by the method as Suggested by USFDA
(http://www.fda.gov/CDER/GUIDANCE/4252fnl.htm)
Lower Limit of Quantification (LLOQ)
The lowest standard on the calibration curve should be accepted as
the limit of quantification if the following conditions are met:
The analyte response at the LLOQ should be at least 5 times the
response compared to blank response.
Analyte peak (response) should be identifiable, discrete, and
reproducible with a precision of 20% and accuracy of 80-120%.
And it has no correlation with Cmax as both are the technical terms
related to different Fields. LLOQ is the term used in Bioanalytical
methods while Cmax is the term related to bioavailability of drug.
Thanks
Regards
VINEET SINGH
Back to the Top
Detection Limit:
refers to the limit to which an analytical signal can be measured and
distinguished from the background noise with a specific level of
confidence in the
observation. The term is probably the most widely abused and least
useful of any in
laboratory literature.
The most common definition of detection limit is the lowest
concentration of an element
that can be detected with a 95% probability. This is calculated by
taking a large number
of instrumental readings at or near the blank level, calculating the
standard deviation and
determining the value corresponding to 2 standard deviations plus the
blank value.
Some can simply say that the LOQ or LOD is Cmax/32 or 64 so they can
get to the concentration representing >90% of the PK profile. This
can be practical but the guidelines were as illustrated above.
I hope this helps.
Murad
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)