Development of a diagnostic screening strategy for niemann-pick diseases based on simultaneous liquid chromatography-tandem mass spectrometry analyses of n-palmitoyl-o-phosphocholine-serine and sphingosylphosphorylcholine

Anna Iwahori, Masamitsu Maekawa, Aya Narita, Akie Kato, Toshihiro Sato, Jiro Ogura, Yu Sato, Masafumi Kikuchi, Atsuko Noguchi, Katsumi Higaki, Torayuki Okuyama, Tsutomu Takahashi, Yoshikatsu Eto, Nariyasu Mano

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Early diagnosis of Niemann-Pick diseases (NPDs) is important for better prognosis of such diseases. N-Palmitoyl-O-phosphocholine-serine (PPCS) is a new NPD biomarker possessing high sensitivity, and with its combination with sphingosylphosphocholine (SPC) it may be possible to distinguish NPD-C from NPD-A/B. In this study, a rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method (method 1) and a validated LC-MS/MS analysis (method 2) of PPCS and SPC were developed, and we have proposed a diagnostic screening strategy for NPDs using a combination of serum PPCS and SPC concentrations. Nexera and API 5000 were used as LC-MS/MS systems. C18 columns with lengths of 10 and 50mm were used for method 1 and 2, respectively. 2H3-Labeled PPCS and nor-SPC were used as internal standards. Selective reaction monitoring in positive-ion mode was used for MS/MS. Run times of 1.2 and 8min were set for methods 1 and 2, respectively. In both methods 1 and 2, two analytes showed high linearity in the range of 1-4000ng/mL. Method 2 provided high accuracy and precision in method validation. Serum concentrations of both analytes were significantly higher in NPD-C patients than those of healthy subjects in both methods. Serum PPCS correlated between methods 1 and 2; however, it was different in the case of SPC. The serum PPCS/SPC ratio was different in healthy subjects, NPD-C, and NPD-A/B. These results suggest that using a combination of the two LC-MS/MS analytical methods for PPCS and SPC is useful for diagnostic screening of NPDs.

Original languageEnglish
Pages (from-to)1398-1406
Number of pages9
JournalBiological and Pharmaceutical Bulletin
Volume43
Issue number9
DOIs
Publication statusPublished - 2020 Sep 1

Keywords

  • Discrimination
  • Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
  • N-palmitoyl-O-phosphocholine-serine
  • Niemann-Pick disease
  • Screening
  • Sphingosylphosphocholine

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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