title: Determination of plasma cholesterol sulfate by LC-APCI-MS/MS in the context of pediatric autism.
abstract: Cholesterol sulfate (CS) has various biological functions. Previously, plasma CS was measured primarily as a means to diagnose X-linked ichthyosis; however, a recent hypothesis suggests that CS deficiency might be related to autism. As such, an assay capable of measuring both very high (in the case of X-linked ichthyosis) and very low (in the case of autism) plasma CS levels is required. Here we describe a novel LC-APCI-MS/MS method for the determination of CS in human plasma, and we propose normal CS ranges for children, based on studies of a local population of normal Chinese children between the ages of 2 and 10. In addition, we have used this method to measure plasma CS in autistic children. CS was isolated by solid-phase extraction, and quantified by isotope-dilution LC-APCI-MS/MS in negative ion mode monitoring 465.3>97.1 m/z (CS) and 472.3>97.1 m/z (CS-d7). Mean recovery of the assay ranged from 88.1 to 112.7%; within- and between-run imprecisions have CVs less than 7.2 and 8.1%, respectively. The assay was linear up to at least 100 µmol L(-1). The reference interval of plasma CS in males (range: 1.16-4.23 µmol L(-1)) was found to be higher than in females (range: 0.86-3.20 µmol L(-1)). Comparison of normal and autistic children showed no statistically significant difference in the plasma CS level. In conclusion, a robust LC-APCI-MS/MS method for plasma CS was developed, and a pediatric reference interval was derived from applying the method to normal and autistic children.
authors.affiliation: Department of Chemistry, Hong Kong Baptist University, Kowloon, HKSAR, Kowloon Tong, PR China; Department of Clinical Biochemistry, Queen Mary Hospital, Pokfulam Road, HKSAR, PR China.
authors.forename: Bonnie Mei-Wah
authors.initials: BM
authors.lastname: Fong
authors.forename: Sidney
authors.initials: S
authors.lastname: Tam
authors.forename: Kelvin Sze-Yin
authors.initials: KS
authors.lastname: Leung
mesh_terms: D001321:Autistic Disorder / Q000097:blood / Q000175:diagnosis; D002138:Calibration; D002648:Child; D002675:Child, Preschool; D002788:Cholesterol Esters / Q000097:blood*; D002853:Chromatography, Liquid / Q000592:standards*; D005260:Female; D006801:Humans; D008297:Male; D012016:Reference Values; D012737:Sex Factors; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry / Q000592:standards*
chemical_list: D002788:Cholesterol Esters; C007045:cholesteryl sulfate
keywords: Autism; Chinese pediatric reference interval; LC–APCI-MS/MS; Plasma cholesterol sulfate