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A simple and rapid method based on liquid chromatography-tandem mass spectrometry for the measurement of α-L-iduronidase activity in dried blood spots: an application to mucopolysaccharidosis I (Hurler) screening.

Abstract：

BACKGROUND:We developed an analytical method to measure α-L-iduronidase (IDUA) activity in dried blood spots. This was achieved by using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with electrospray ionization in the positive ion mode. METHODS:Chromatographic separation was completed using mobile phase involving water-formic acid and acetonitrile-formic acid over 2.8 min of run time on a column with a Kinetex XB-C18 (Phenomenex, USA). The detection of column effluent was performed using a Xevo TQ-S triple quadrupole mass spectrometer (Waters, USA) in the multiple-reaction monitoring mode. This method was verified with blank and control samples at four activity levels: base, low, medium, and high. Control materials were provided from Centers for Disease Control and Prevention (CDC). RESULTS:Intra- and inter-day precisions were between 2.6% and 16.5% and between 7.9% and 17.0%, respectively. A correlative regression study on the IDUA activity in CDC-control samples performed to assess the validity of the developed method showed a highly significant linear association (r(2)=0.9976) between the calculated and CDC-reported values and an obvious difference in activity among the four levels. This reliable analytical method was applied to mucopolysaccharidosis I (Hurler) screening of patients under treatment (n=4) and in normal controls (n=129). IDUA activity ranged from 8.98 to 77.12 µmol/hr/L) in normal controls, and patients undergoing medical treatment showed low IDUA activity. CONCLUSIONS:This method had advantages of simplicity, rapid sample preparation, and liquid chromatographic separation, which efficiently inhibited ionization suppression induced by matrix effects in mass spectrometric detection.

journal_name

Ann Lab Med

journal_title

Annals of laboratory medicine

authors

Yang JS,Min HK,Oh HJ,Woo HI,Lee SY,Kim JW,Song J,Park HD

doi

10.3343/alm.2015.35.1.41

keywords:

["Iduronidase","Mass spectrometry","Mucopolysaccharidosis I"]

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

41-9

issue

1

eissn

2234-3806

issn

2234-3814

journal_volume

35

pub_type

杂志文章

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