Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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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

  • Yang, Jeong Soo (Clinical Trial Center, Clinical Research Institute, Samsung Medical Center) ;
  • Min, Hye Kyeong (Clinical Trial Center, Clinical Research Institute, Samsung Medical Center) ;
  • Oh, Hyeon Ju (Department of Laboratory Medicine and Genetics, Samsung Medical Center) ;
  • Woo, Hye In (Department of Laboratory Medicine and Genetics, Samsung Medical Center) ;
  • Lee, Soo-Youn (Clinical Trial Center, Clinical Research Institute, Samsung Medical Center) ;
  • Kim, Jong-Won (Department of Laboratory Medicine and Genetics, Samsung Medical Center) ;
  • Song, Junghan (Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital) ;
  • Park, Hyung-Doo (Department of Laboratory Medicine and Genetics, Samsung Medical Center)
  • Received : 2013.11.06
  • Accepted : 2014.10.02
  • Published : 2015.01.02
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Abstract

Background: We developed an analytical method to measure ${\alpha}$-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 $77.12{\mu}mol/hr/L$) 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.

Keywords

Acknowledgement

Supported by : Ministry of Health and Welfare

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