Rapid quantitation of globotriaosylceramide in human plasma and urine: a potential application for monitoring enzyme replacement therapy in Anderson-Fabry disease.
A method for measuring globotriaosylceramide (Gb3, or GL3) levels in plasma and urine of humans affected by Anderson-Fabry disease has been developed. The analyses are performed using flow injection analysis-electrospray ionization-tandem mass spectrometry (FIA-ESI-MS/MS). The method is rapid, sensitive and hence suitable for high-throughput analyses, requiring only a simple 50-fold dilution for the preparation of plasma and urine samples. The detection of the analytes of interest was achieved using a triple quadrupole instrument operating in the multiple reaction monitoring mode. The linearity of the calibration standard responses, the intra- and inter-assay precision, the accuracy and the detection limit of the method were evaluated. The proposed method allows a rapid and accurate assessment of globotriaosylceramide in biological samples. Data obtained from healthy volunteers and Anderson-Fabry affected subjects suggest a potential role for this technique in monitoring the effectiveness of Anderson-Fabry disease therapy. The results obtained in two actual cases treated with enzyme replacement therapy are reported and discussed.
Boscaro
Francesca
F
Centro Interdipartimentale di Spettrometria di Massa, Università di Firenze, Viale G. Pieraccini 6, 50139 Firenze, Italy.
Pieraccini
Giuseppe
G
la Marca
Giancarlo
G
Bartolucci
Gianluca
G
Luceri
Cristina
C
Luceri
Francesca
F
Moneti
Gloriano
G
D000795:Fabry Disease / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods* / Q000592:standards; D013696:Temperature; D014281:Trihexosylceramides / Q000032:analysis* / Q000097:blood / Q000652:urine; D000519:alpha-Galactosidase / Q000627:therapeutic use*
D011994:Recombinant Proteins; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D000519:alpha-Galactosidase