In Vitro and In Vivo Study of Neurotherapeutic Molecules by Tandem Mass Spectrometry

Abstract

Neurological disorders may cause various disabilities. The mechanism of neurologicaldisorders may attribute to neuronal, structural, electrical, or molecular abnormalities. Many therapies such as surgery, deep brain/spinal cord stimulation are invasive treatments but with amazing treatment results. More common therapy of various types of medicine is the main method for clinical application. This work focuses on a few types of therapeutic neuroactive molecules and aims to investigate the In vitro and In vivo properties. Chapter 1 will introduce the principles of classic neurological disorders and the current common detection methods for neurotransmitters and peptides. Chapter 2 will introduce the method development of nano liquid chromatography coupled to tandem mass spectrometry for a better analysis of low abundance neurotherapeutic molecules. Chapter 3 will investigate the In vitro stability improvement of four types of glycosylated peptide-based drugs. Chapter 4 will investigate the improvement of In vivo stability and blood brain barrier (BBB) transmission of glycosylated neuroactive peptide-based drugs with developed online-preservation microdialysis coupled to liquid chromatography tandem mass spectrometry technique. We also studied the impact of micelle-assisted drug delivery formula for improved bioavailability. Chapter 5 will introduce the small neuroactive molecule, ketamine and its application in the treatment of LID. We studied the pharmacokinetic profile of single injection and infusion injection in the rat model and human model respectively. Chapter 6 will conclude the work and introduce the future directions of more therapeutic neuroactive peptides.