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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.

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 mm and 50 mm were used for method 1 and 2, respectively. 2H3-labeled PPCS (PPCS-2H3_ 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 min 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.