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Newborn screening for 3-hydroxy-3-methylglutaric aciduria using direct analysis in real-time mass spectrometry.
Journal of Mass Spectrometry : JMS 2018 November 24
A novel method utilizing ambient thermal desorption ionization with a direct analysis in real-time source integrated with mass spectrometry (DART-MS) was established and applied to the rapid analysis of 3-hydroxy-3-methylglutaric (3-HMG) acid in the neonatal urine. Instrument parameter settings were optimized to obtain high sensitive and accurate determination of 3-HMG acid. The use of helium gas heated to temperature of 400 o C was observed to permit deprotonation, 3-HMG acid producing a abundant [M-H]- (m/z 161) in the negative ion mode. The calibration curve was determined to be linear over the range of 0.05-5 mg/L, with the correlation coefficient r = 0.9988 and the relative standard deviations (n=6) in the range of 1.5 to 11.8%. The limit of detection was 0.002 mg/L and the limit of quantitation was 0.007 mg/L. The recoveries ranged from 88.0% to 123.1%. Four urine samples from patients and four simulated urine samples were investigated. The results of DART-MS were in agreement with the values determined using established methods at the hospitals. The proposed method demonstrated significant potential in the application of the high-throughput screening in newborn screening.
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