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The following message was posted to: PharmPK
Dear group,
I would like to have an understanding on the view of regulatory
authority on using the adduct for the quantitation of any compound
from biological matrix. If adducts (eg., Na+ (+23) or K+ (+ 39) are
used for the quantitation by LC-MS/MS for any BA/BE study, whether the
regulatory will accept it ???
As per my understanding, in biological matrices where sodium ions are
in plenty, it is scientifically justified to use Na+ of parent
molecules for quantitation. As long as the adducts are stable in the
gaseous phase.
I would appreciate for group's response on this topic.
Regards,
Ravi
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The following message was posted to: PharmPK
Ravi,
No direct experience, but I doubt the metal adducts should be treated
differently from your typical H+ or NH+ counterparts provided you can
validate the method, as these are all quasi-molecular ions.
Jack
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Ravi,
I believe there is no mention of any specific allowed or disallowed
precursor/product ions in any regulatory guidance, but you may want to
contact the regulatory authority you will be dealing with directly,
and ask them, just to make sure there are no surprises. Personally, I
have used ammonium adduct of cyclosporin as a parent ion (intact
cyclosporin being the "product" ion) without any problem.
Andrew Volosov
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Ravi
I think you can do it without any problem. As long as the method is
accurate, precise and robust and validated as per the regulatory
requirements i do not foresee any issues. But you could request a
controlled correspondence to the Agency to be on the safe side.
Good Luck
Manish Issar, Ph.D
Applied Biopharmaceutics
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The following message was posted to: PharmPK
If you validate against this adduct and all exercises of the validation
pass, the adduct is then the only form to be used.
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Hi Ravi,
As pointed out by others, regulator will not bother on what ions you
use, as long as you adhere to guidelines. In fact, some time it will
be prudent to consider other adduct ions to get better sensitivity
than routine M+H or M-H.
Regards,
Vinayak
Vinayak Nadiger
Manager , Bioanalytical Chemistry
11 Biopolis Way, Helios #08-05
Singapore 138667
E Mail: vnadiger.-a-.combinatorx.com
Website:www.combinatorx.com
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The following message was posted to: PharmPK
Dear Ravi
First try to stop the adduct formation if possible. If not than
validate the method as per regulatory requirement, and proceed for
your analysis and also inform to your regulatory department for safer
side.
Concern other PK member response also on this topic.
May be this helps to you.
Good Luck
laxman kaswan
LifeSan Clinical Research
Mumbai INDIA
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Yes Quantitation by adduct is accepted by regulatory We have
experience for the same
Regards,
Pravin S. Patil, MSc.Ph.D.
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