HILIC-UHPLC-QTRAP®/MS2 quantification of 15 neurotransmitters of the combination of donepezil and ginkgo ketoester tablet in different biological matrices from dementia mice: Application to study the synergistic effect of the two drugs

Abstract Neurotransmitters (NTs) were signaling molecules which played a key role in the communication of nerve cells. Simultaneous monitoring of NTs possessed important scientific significance for dementia related pharmacology, pathology and drug study. This study developed an effective method for analysis of 15 underivatized NTs on hydrophilic interaction ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (HILIC-UHPLC-QTRAP®/MS2). Under the optimized chromatographic conditions, good separation of 15 NTs was achieved within 5.0 min. The developed HILIC-UHPLC-QTRAP®/MS2 was validated by matrix effects, linearity, limits of detections and quantifications, precision, stability and recovery. Finally, the validated analytical method was applied to quantify 15 NTs in brain, plasma, intestinal and intestinal contents from normal, dementia model and the combination of ginkgo ketoester tablet (GT) and donepezil drug-administered mice. The result showed that some NTs such as γ-aminobutyric acid, acetylcholine and glutamic acid presented significant differences in the same biological matrix with different doses of the combination of GT and donepezil. In addition, based on the theory of “brain-gut-microbiome” axis, the combination of GT and donepezil with one time of clinical equivalent dose exhibited a synergistic anti-dementia effect by regulating the disordered NTs to normal levels in different biological matrices. In summary, the presented HILIC-UHPLC-QTRAP®/MS2 method might be used to monitor NTs from different clinical biological fluids in the further study.