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DETERMINATION OF RIMONABANT THIOPHENE ANALOGUES IN RAT PLASMA AND BRAIN BY LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY (Abstract/Poster in atti di convegno)

Type

Abstract/Poster in atti di convegno (Classe)
Prodotto della ricerca (Classe)

Label

DETERMINATION OF RIMONABANT THIOPHENE ANALOGUES IN RAT PLASMA AND BRAIN BY LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY (Abstract/Poster in atti di convegno) (literal)

Anno

2008-01-01T00:00:00+01:00 (literal)

Alternative label

Peddio G.,Pittau B.,Piras S, Lazzari P. Pani L. (2008)
DETERMINATION OF RIMONABANT THIOPHENE ANALOGUES IN RAT PLASMA AND BRAIN BY LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY
in The 18th Annual Symposium of the International Cannabinoid Research Society, Aviemore, GB
(literal)

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Peddio G.,Pittau B.,Piras S, Lazzari P. Pani L. (literal)

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Introduction: Rimonabant and other pyrazole derivatives have been widely studied for their CB1 antagonism in different in vitro and in vivo models. The lead compound has been successfully employed in human as anti-obesity drug. In order to evaluate structure-activity relationship due to the modification of the different substituents at the various position of the pyrazole core, a new series of cannabinoid pyrazole derivatives have been recently obtained by PharmaNess. Among these new class of compounds, we have synthesized thiophene substituted analogues of Rimonabant (i.e. NESS006A, and NESS014A). To evaluate pharmacokinetic profile and brain absorption of these compounds, we have developed in this study new HPLC-MS/MS based methods. Methods: A HPLC system (Waters separation module Alliance 2695) was used to inject 5µl aliquots of processed samples. The chromatographic was performed using Xbridge C18 2.1*100, 3.5um, at 35°C. HPLC mobile phase flow rate was set at 0.2 ml/min, with gradient elution starting at 10% acetonitrile and 90% water (0.1% formic acid), followed by a linear increase of acetonitrile composition to 100%. Quantification was achieved by multiple reaction monitoring (MRM) detection in the positive ion electrospray, using a Quattro Micro triple quadrupole mass spectrometer (Micromass, Waters). The source condition were as follows: Capillary voltage 1kV, Source temperature 120°C, Desolvation temperature 350°C, Desolvation gas flow 800L/min, Cone gas flow 50L/h, Collision cell pressure 3.2 e-3 mbar, Dwell time 0.1 sec, Inter-Scan delay 0.1 sec, Inter-Channel delay 0.02 sec. The precursor product ions pairs monitored were: 463.3> 362.9, 469.1> 368.8 and 469.1> 382.9 respectively for SR141716A, NES006A, and NESS014A. Standard stock solutions (1mg/ml) of SR141716A, NESS006, and NESS014 were prepared in methanol. Analytical standard samples were prepared by spiking known quantity of standard solutions into blank rat plasma and brain. The plasma and homogenate brain samples were purified using protein precipitation technique and solid-phase extraction. Results: LC-MS/MS identified methods demonstrate no interfering peak from endogenous components in studied complex biological samples. For all the assayed derivatives the method is sensitive and specific starting from both rat plasma and brain. Conclusion: HPLC-MS/MS based procedures have been optimized to determine cannabinoid thiophene-pyrazole derivative levels in both rat plasma and brain. (literal)

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