Quantitative determination of guanidinoacetate and creatine in dried blood spot by flow injection analysis-electrospray tandem mass spectrometry

被引:46
作者
Carducci, C
Santagata, S
Leuzzi, V
Carducci, C
Artiola, C
Giovanniello, T
Batti, R
Antonozzi, I
机构
[1] Univ Roma La Sapienza, Dipartimento Med Sperimentale & Patol, I-00161 Rome, Italy
[2] Univ Roma La Sapienza, Dipartimento Sci Neurobiol & Psichiat Eta Evolut, I-00185 Rome, Italy
[3] Univ Pisa, Ist Stella Maris, Div Neuropsichiat Infantile, I-56021 Pisa, Italy
关键词
guanidinoacetate; creatine; tandem mass spectrometry; dried blood spot; GAMT; AGAT;
D O I
10.1016/j.cca.2005.06.016
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Background: Guarudinoacetate (GAA) and creatine (Cr) are reliable biochemical markers of primary creatine disorders. The aim of this study was to develop and validate a method for the determination of GAA and Cr in dried blood spot through the use of stable isotope dilution and flow injection analysis (FIA)-ESI-MS/MS. Methods: Dried blood spots were extracted using methanol-water solution containing D3-Cr. After evaporation and formation of butyl esters, samples were analyzed using multiple reaction monitoring mode (m/z 174.2 --> 101.1 for GAA, 188.3 --> 90.1 for Cr and 191.3 --> 93.1 for D3-Cr). Results: The analysis was very fast (1 min). The detection limits were 0.34 mu mol/l of blood and 0.30 mu mol/l of blood for Cr and GAA, respectively, and the response was linear over the range 0.25-12.5 mu mol/l of blood for GAA and 3.57-624.7 mu mol/l of blood for Cr. Recovery range was 93-101% for Cr and 94-105% for GAA and between-run CVs were 5.3% for GAA and 4.5% for Cr. Ion suppression effect was also studied. The method was applied to spots obtained from two patients affected by GAMT deficiency, four patients affected by AGAT deficiency (including a newborn) as well as 282 healthy subjects. Conclusions: The detection of GAA in dried blood spot by FIA-ESI-MS/MS is a highly reliable and high throughput method for the diagnosis of GAMT and AGAT deficiencies and a possible tool for newborn screening of both these tractable disorders. (C) 2005 Elsevier B.V All rights reserved.
引用
收藏
页码:180 / 187
页数:8
相关论文
共 27 条
[1]   Creatine and guanidinoacetate: diagnostic markers for inborn errors in creatine biosynthesis and transport [J].
Almeida, LS ;
Verhoeven, NM ;
Roos, B ;
Valongo, C ;
Cardoso, ML ;
Vilarinho, L ;
Salomons, GS ;
Jakobs, C .
MOLECULAR GENETICS AND METABOLISM, 2004, 82 (03) :214-219
[2]   Ion suppression in mass spectrometry [J].
Annesley, TM .
CLINICAL CHEMISTRY, 2003, 49 (07) :1041-1044
[3]   Creatine depletion in a new case with AGAT deficiency:: clinical and genetic study in a large pedigree [J].
Battini, R ;
Leuzzi, V ;
Carducci, C ;
Tosetti, M ;
Bianchi, MC ;
Item, CB ;
Stöckler-Ipsiroglu, S ;
Cioni, G .
MOLECULAR GENETICS AND METABOLISM, 2002, 77 (04) :326-331
[4]  
BATTINI R, 2004, J INHER METAB DIS S1, V27, P214
[5]   Analysis of guanidinoacetate and creatine by isotope dilution electrospray tandem mass spectrometry [J].
Bodamer, OA ;
Bloesch, SM ;
Gregg, AR ;
Stockler-Ipsiroglu, S ;
O'Brien, WE .
CLINICA CHIMICA ACTA, 2001, 308 (1-2) :173-178
[6]   Quantitation of SR 27417 in human plasma using electrospray liquid chromatography tandem mass spectrometry: A study of ion suppression [J].
Buhrman, DL ;
Price, PI ;
Rudewicz, PJ .
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, 1996, 7 (11) :1099-1105
[7]  
Carducci C, 2002, CLIN CHEM, V48, P1772
[8]   Automated high-performance liquid chromatographic method for the determination of guanidinoacetic acid in dried blood spots: a tool for early diagnosis of guanidinoacetate methyltransferase deficiency [J].
Carducci, C ;
Birarelli, M ;
Santagata, P ;
Leuzzi, V ;
Carducci, C ;
Antonozzi, I .
JOURNAL OF CHROMATOGRAPHY B, 2001, 755 (1-2) :343-348
[9]   Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns [J].
Chace, DH ;
Kalas, TA ;
Naylor, EW .
CLINICAL CHEMISTRY, 2003, 49 (11) :1797-1817
[10]   Determination of guanidinoacetate and creatine in urine and plasma by liquid chromatography-tandem mass spectrometry [J].
Cognat, SB ;
Cheillan, D ;
Piraud, M ;
Roos, B ;
Jakobs, C ;
Viany-Saban, C .
CLINICAL CHEMISTRY, 2004, 50 (08) :1459-1461