Developing chromatography-mass spectrometry techniques for quantitative determination of the new original neuroleptic drug dilept

Abstract

Gas chromatography-mass spectrometry (GC-MS) and HPLC-MS techniques have been developed for studying fragmentation and determining the main ion species in the mass spectra of the new original neuroleptic dilept (N-caproyl-L-prolyl-L-tyrosine methyl ester) and its expected metabolites N-caproyl-L-prolyl-L-tyrosine (M1) and N-caproyl-L-proline (M2). Trimethylsilyl derivatives of dilept and its metabolites were analyzed using GC-MS and HPLC-MS in both positive-and negative-ion modes. Retention times were determined. The EI-MS, ESI-MS, and ESI-MS/MS spectra of all substances were obtained. Results of a comparative analysis of the chromatographic data show that the HPLC-ESI-MS/MS method in negative-ion mode is most sensitive to dilept (LOD = 0.5 ng/mL) and can be recommended for subsequent investigations of metabolism and pharmacokinetics of this potential neuroleptic drug.

Molecular-biological problems of drug design and mechanism of drug action

“…We used HPLC-(-)ESI-MS and HPLC-(-)ESI-MS/MS methods that have been previously described [7] to determine dilept and its metabolites in rat blood plasma. It was found that dilept forms a demethylated metabolite upon addition to rat blood plasma.…”

Permeability of the Blood-Brain Barrier for Dilept and Its Active Metabolite

“…Dry residue was dissolved in 50 μl methanol and analyzed by HPLC-MS/MS (MS: mass spectrometry). Plasma and brain levels of dilept and its metabolite were measured by previously developed HPLC-MS/MS [1]. Penetration through BBB was evaluated by coeffi cient of distribution for the studied compounds (K brain/plasma ).…”