Tackling the Orexin Conundrum: An Optimized LC–MS/MS Method Demonstrates Accurate CSF Quantification and Absence in Peripheral Blood

Analytical Chemistry 2026

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Authors: Yan Cao, Y M Zhang, J Y Han, Zhengwen Xu, Huimin Zhang, Y L Yang, Dong Wang, Yanhong Zhai, Shuqin Zhan, Hui Li, Zhu Cao
DOI: 10.1021/acs.analchem.6c00454
Cited by: 1
References: 23

Abstract

Cerebrospinal fluid (CSF) orexin-A is the gold-standard biomarker for narcolepsy type 1 (NT1), however, conventional radioimmunoassays (RIA) often suffer from cross-reactivity and overestimation, fueling long-standing conundrum regarding orexin detection in peripheral blood. In this study, we developed an ultrasensitive LC–MS/MS method (LLOQ = 0.1 pg/mL) incorporating a streamlined one-step protein precipitation protocol coupled with acid-shielding and cocktail-protection strategies to mitigate severe nonspecific adsorption and enzymatic degradation. Verification in paired CSF and blood samples from narcolepsy patients and controls revealed that orexin-B and peripheral orexins remain consistently below the detection limit (

Fields of Study & Subjects

Sleep and Wakefulness Research Sleep and Work-Related Fatigue Obstructive Sleep Apnea Research

Publication details

Journal / source
Analytical Chemistry
Publisher
American Chemical Society (ACS)
Volume
98
Issue
20
Pages
14958–14966
Publication date
12 May 2026
Language
EN