Sensitive LC-MS/MS method for quantitation of levodopa and carbidopa in plasma: application to a pharmacokinetic study.

AIM: The combination of levodopa with carbidopa has been used for treatment of Parkinson's disease being an important therapy in dopamine level control in the brain. Both are very polar compounds becoming a challenge for analysis by LC-MS/MS. MATERIALS & METHODS: In this work, it was developed and validated a sensitive bioanalytical method by UHPLC-MS/MS for simultaneous levodopa and carbidopa quantification in human plasma using a fast protein precipitation method. Moreover, the bioanalytical method was applied to a pharmacokinetic study in healthy volunteers. RESULTS/CONCLUSION: The results demonstrated a sensitive and adequate method for application to pharmacokinetic/bioequivalence studies.

Exploring the coordination chemistry of isomerizable terpyridine derivatives for successful analyses of cis and trans isomers by travelling wave ion mobility mass spectrometry.

The photochemical cis-trans isomerization of the 4-{4-[2-(pyridin-4-yl)ethenyl]phenyl}-2,2':6',2''-terpyridine ligand (vpytpy) was investigated by UV-vis, NMR and TWIM-MS. Ion mobility mass spectrometry was performed pursuing the quantification of the isomeric composition during photolysis, however an in-source trans-to-cis isomerization process was observed. In order to overcome this inherent phenomenon, the isomerization of the vpytpy species was suppressed by complexation, reacting with iron(II) ions, and forming the [Fe(vpytpy)(2)](2+) complex. The strategy of "freezing" the cis-trans isomerizable ligand at a given geometric conformation was effective, preventing further isomerization, thus allowing the distinction of each one of the isomers in the photolysed mixture. In addition, the experimental drift times were related to the calculated surface areas of the three possible cis-cis, cis-trans and trans-trans iron(II) complex isomers. The stabilization of the ligand in a given conformation also allows us to obtain the cis-cis and cis-trans complexes exhibiting the ligand in the metastable cis-conformation, as well as in the thermodynamically stable trans-conformation.