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Dear all,
I am facing a difficulty in extraction of Zanamvir from Serum. The
Zanamvir having carboxylic and guanidine groups in structure and its
having 5 - 10% protein binding capacity and it is more Polar compound.
We have tried exctraction with SPE with different catridges like MCX,
SAX and HLB and Precipitation with Acetonitrile, TCA, methanol and
tried with different LLE also (with acidification and basification
also). but we are not getting even 1% recovery. We are working LCMS/MS
with ACN:Water:Formic acid as mobile phase Please give a suggestions
Thanks and regards
Venkat
Nektar therapeutics
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Dear Venki
Add strong acid to sample like 1 N HCL and then take SPE method with
HLB it will work. Do elution with 1% Formic acid in methanol. you
check from 0.1% to 1% FA in MEOH and find out in which you are
getting best recovery. Take Xtera MS 50 mm column. and 80:20 Meoh : 2
mm Ammonium Acetate buffer. I have worked on similar category compound
earlier with this method and has given me good recovery and good
reproducibility. Remember to give at list 3 ml Water wash to cartridge
after loading of sample on cartridge other wise HCL will come in
sample and will be harmful to MS.
Regards
Bhavesh Patel
Assistat Manager
Pharmacokinetics
Sun Pharmaceutical Industries Ltd.
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The following message was posted to: PharmPK
Dear Venkat
In reply to your problem regarding extraction of zanamavir, a
neuroamidase inhibitor. As per literature, the other structurally
similar drug to Zanamvir is oseltamivir. In vitro metabolic studies of
oseltamivir in rat revealed a carboxylic metabolite. To prevent
oseltamivir conversion to metabolite during extraction, normally in the
extraction tubes a substance named 'dichlorvos' is employed. Dichlorvos
prevents the conversion by blocking plasma esterases. So as zanamvir
belongs to the same category, there is a possibility of conversion by
similar enzymes and ultimately leading to poor recovery. So you may go
through literature related to metabolism of zanamvir. In oseltamivir,
normally methanol is employed in mobile phase for efficient separation.
So you may employ methanol in mobile phase and can also try
precipitation technique using methanol. I advise you to try doing
initial recovery experiments at higher levels for better understanding.
You may refer the following reference for more details
http://aac.asm.org/cgi/content/abstract/AAC.01534-06v1
Hope this helps.
Regards
Pradeep Singh Rawat
Research Scientist
Metabolism & Pharmacokinetics Department
Ranbaxy Research Laboratories
India
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