标题：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
摘要：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 50 mm 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 8 min were set for methods 1 and 2, respectively.In both methods 1 and 2, two analytes showed high linearity in the range of 1–4000 ng/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.
关键词：Niemann–Pick disease;screening;discrimination;liquid chromatography-tandem mass spectrometry (LC-MS/MS);N-palmitoyl-O-phosphocholine-serine;sphingosylphosphocholine
