title: 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.
authors.affiliation: Clinical Trial Center, Clinical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Jeong Soo
authors.initials: JS
authors.lastname: Yang
authors.affiliation: Clinical Trial Center, Clinical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Hye Kyeong
authors.initials: HK
authors.lastname: Min
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Seoul, Korea.
authors.forename: Hyeon Ju
authors.initials: HJ
authors.lastname: Oh
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Seoul, Korea. ; Department of Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hye In
authors.initials: HI
authors.lastname: Woo
authors.affiliation: Clinical Trial Center, Clinical Research Institute, Samsung Medical Center, Seoul, Korea. ; Department of Laboratory Medicine and Genetics, Samsung Medical Center, Seoul, Korea. ; Department of Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Seoul, Korea. ; Department of Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Junghan
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Seoul, Korea. ; Department of Laboratory Medicine and Genetics, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyung-Doo
authors.initials: HD
authors.lastname: Park
mesh_terms: D002851:Chromatography, High Pressure Liquid; D059788:Dried Blood Spot Testing / Q000295:instrumentation*; D006801:Humans; D007068:Iduronidase / Q000032:analysis* / Q000378:metabolism; D008059:Mucopolysaccharidosis I / Q000097:blood / Q000175:diagnosis*; D012044:Regression Analysis; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D007068:Iduronidase
keywords: Iduronidase; Mass spectrometry; Mucopolysaccharidosis I