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Dear All
We are working on aspirin also its metabolite salicylic acid (LCMS).
Problem we are facing is that the compound gets disintegrated in
source itself, to salicylic acid-- it gives salicylic acid peak in Q1
scan only (that is we are getting 2 peaks for aspirin, in Q1). This is
the case inspite of the fact that we have optimized all parameters
upto their minimum status, but the situation persists.
Aspirin (acetyl salicylic acid) is getting converted to salicylic acid
(40-50%) thruout the linearity in source itself.
Aspirin stock is in 2 % Formic acid in methanol stored in -70 stable
for 48 hrs at room temp.
Mobile phase : ACN: 0.2% Acetic acid (90:10)
Column: X-tera rp 18 (4.6*50).
Also we are trying this method in HPLC , there we are getting only 1
peak for aspirin , that is no conversion to salicylic acid-- hence we
have concluded that in MS-- aspirin is getting partially converted to
salicylic acid in source.
Please let us know how to avoid this source induced dissociation. Or
if the members can help regarding the method for analysis of aspirin.
Regards
Ranvijay
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Hi, Ranvijay
Aspirin is difficult to develop on LC-MS/MS due to its conversion to
its metabolite Salicylic Acid. But you can use some additive
(stabilizing Agent) in stock solution preparation to prevent this
conversion or you can do by adduct formatiom.
With Regards
Kintan Patel
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Dear Ranvijay
Source degradation or conversion of aspirin to salicylic acid might be
due to diluent for tuning solution or due to temperature.
If you have water in diluent, you may try using pure organic solvent
for tuning to prevent hydrolysis of aspirin to salicylic acid.
Temperature can be another reason for degradation (A more than
fivefold increase in the hydrolysis of aspirin was noted when the
temperature was raised to 37* from 22.5*). If temperature is an issue,
you can try APCI rather than ESI, as it is more suitable for thermo
labile compounds.
You may go through the following reference.
Shamsul K. Bakar, Sarfaraz Niazi. Stability of aspirin in different
media. Journal of Pharmaceutical Sciences. Volume 72 Issue 9, Pages
1024 - 1026, 2006
Please go through the recent article (June 2008) where authors have
developed aspirin method by LC/MS
Bae SK, Seo KA, Jung EJ, Kim HS Et al. Determination of
acetylsalicylic acid and its major metabolite, salicylic acid, in
human plasma using liquid chromatography-tandem mass spectrometry:
application to pharmacokinetic study of Astrix in Korean healthy
volunteers. Biomed Chromatogr. 2008 Jun;22(6):590-5)
Hope this helps
Regards
Pradeep Singh Rawat,
Research Scientist,
Metabolism and Pharmacokinetics Department,
Ranbaxy Research Laboratories,
India.
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Dear All
In response to the posting by Ranvijay Singh, I offer the following:
Aspirin is highly unstable to esterase activity and esterases are
present in many tissues including blood. This problem may be minimised
with the addition of physostigmine which will ensure insignificant
hydrolysis during storage and analysis of samples.
Aspirin can be effectively quantified after separation from salicylic
acid by HPLC. Once the aspirin has been eluted off the column, it can
be rapidly hydrolysed to salicylic acid in the presence of strong
base, then run through a fluorescence detector. This method can
achieve a lower limit of quantitation around 1 ng/mL. This limit was
sufficient to quantify aspirin after 50 mg doses after intravenous
administration and oral administration of a solution. Even more
impressive was adequate quantitation of aspirin 6 to 7 h following 50
mg of a sustained release formulation to healthy volunteers. For
further reading, see (1) Siebert and Bochner (1987) Determination of
plasma aspirin and salicylic acid concentrations after low aspirin
doses by high performance liquid chromatography with post column
hydrolysis and fluorescence detection, J Chromatogr, 420: 425 - 431
and (2) Bochner et al (1988) Pharmacokinetics of low-dose oral
modified release, soluble and intravenous aspirin in man, and effects
on platelet function, Eur J Clin Pharmacol, 35:287 - 294.
I am not sure what the statement "getting converted to salicylic
acid .... throughout the linearity in source itself" means.
Des Williams
--
Des Williams, PhD, FRACI
Sansom Institute
School of Pharmacy and Medical Sciences
University of South Australia
North Terrace
Adelaide
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Dear all,
Do you think that physostigmine could also be used for other compounds
highly unstable to esterase activity in plasma ?
Thank you for your answer.
Philippe BIRCKEL
Bioanalytical Chemistry
AVOGADRO
Parc de Genibrat
31470 Fontenilles
email philippe.birckel.aaa.avogadro.fr
internet www.avogadro-lab.com
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PMSF and Pefabloc are other esterase inhibitors that can be used and are
probably less toxic than physostigmine. Using sodium fluoride/EDTA
anticoagulant may also be useful.
Jonathan Scott
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