Novel GC MS/MS method for bioanalysis of pyrroloquinoline quinone, a potential cognitive enhancer in mice brains

Phenolic compounds have neuroprotective effect in diseases of cognitive impairment. Pyrroloquinoline quinone (PQQ), an aromatic water-soluble quinone enhances cognitive function in-vivo as previously demonstrated by our research group. In an attempt to comprehend the mechanism of action, development of a bioanalytical method for PQQ in brain matrix was essential to investigate blood-brain barrier (BBB) permeability for the drug and/or its metabolites. This study documents a novel fast GCMS/MS method for bioanalysis of PQQ in mice brains following a novel derivatization reaction of this drug. A simple extraction methodology using a single solvent highlights sustainability and greenness of our sample preparation protocol. Method validation and quantitative analysis of PQQ as an intact molecule in mice brain homogenates was done using novel qualifier and quantifier ions of the silylated drug for the first time. We report BBB permeation to PQQ in an induced neuroinflammation mouse model in addition to its sulfate metabolite following intraperitoneal injection. Interestingly, PQQ was detected in brains of control mice on standard diet containing soybeans. In silico prediction suggests the involvement of P-gp in active transport of PQQ across BBB where the drug appears to be is an excellent substrate and inhibitor. Pharmacokinetic analysis in brain revealed t_max as 2 h. Our optimized extraction method, as well as the GC-MS/MS method can be used to quantify levels of PQQ in various matrices opening the door to many Other studies on this polyphenol. Moreover, we recommend the use of PQQ as a co-treatment in cognitive impairment diseases.

Blood brain barrier; GCMSMS; In vivo; Neuroprotection; Pharmacokinetics; Pyrroloquinoline quinone; Silylation.