Determination of Guanidinoacetic Acid in Urine by HPLC-FLD Method

Yıl 2024, Cilt: 3 Sayı: 1, 161 - 166, 25.04.2024

Mehmet Şerif Cansever Esra İşat

Öz

Creatine deficiency syndromes are newly recognized inherited metabolic disorders. Creatine is classified into three groups according to the synthesis steps: guanidinoacetate N-methyl transferase (GAMT) deficiency, arginine-glycine amidinotransferase (AGAT) deficiency, and creatine transporter disorder. Clinically, mental retardation, speech delay, epilepsy, movement, and behavioral disorders are prominent. The common biochemical finding in all three diseases is cerebral creatine deficiency. Low urinary guanidinoacetate (GAA) levels are observed in AGAT deficiency and high urinary GAA levels are observed in GAMT deficiency. In this study, we developed a new, simple, inexpensive, and rapid chromatographic analysis method for the quantitative determination of guanidinoacetate in urine samples. Guanidinoacetate was chromatographically separated with a buffer containing 50 mM formic acid and methanol, 1.0 mL/min flow, C18 (150 mm 4.6 mm, 5.0 µm) analytical column and fluorescence detector at ƛex: 390 nm, ƛem: 470 nm.

Anahtar Kelimeler

guanidinoacetate, creatine, HPLC-FLD

Etik Beyan

Ethics commitee approval of not required in this study

Destekleyen Kurum

No

Kaynakça

• Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol rev., 2000;80(3):1107-213.
• Ohtsuki S, Tachikawa M, Takanaga H, Shimizu H, Watanabe M, Hosoya K, et al. The blood-brain barrier creatine transporter is a major pathway for supplying creatine to the brain. J Cereb Blood Flow Metab., 2002;22(11):1327-35.
• Wyss M, Smeitink J, Wevers RA, Wallimann T. Mitochondrial creatine kinase: a key enzyme of aerobic energy metabolism. Biochim Biophys Acta., 1992;1102(2):119-66.
• Wallimann T, Tokarska-Schlattner M, Schlattner U. The creatine kinase system and pleiotropic effects of creatine. Amino Acids., 2011;40(5):1271-96.
• Brosnan JT, Brosnan ME. Creatine: endogenous metabolite, dietary, and therapeutic supplement. Annu rev Nutr., 2007;27:241-61.
• Stockler-Ipsiroglu S, Apatean D, Battini R, DeBrosse S, Dessoffy K, Edvardson S, et al. Arginine:glycine amidinotransferase (AGAT) deficiency: Clinical features and long term outcomes in 16 patients diagnosed worldwide. Mol Genet Metab., 2015;116(4):252-9.
• Item CB, Stöckler-Ipsiroglu S, StrombergerC, Mühl A, Alessandrì MG, Bianchi MC, et al Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am j Hum Genet., 2001;69(5):1127-33.
• Verhoeven NM, schor Ds, Roos B, Battini R, Stöckler-Ipsiroglu S, Salomons GS, et al Diagnostic enzyme assay that uses stableisotope-labeled substrates to detect larginine:glycine amidinotransferase deficiency. Clin Chem., 2003;49(5):803-5.
• Mercimek-Andrews S, Salomons GS. Creatine Deficiency Disorders. 2009 Jan 15 [updated 2022 Feb 10]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean Li H, Gripp KW, et al, eds. Genereviews® [Internet]. Seattle (WA): university of Washington, Seattle; 1993-2023.
• Mulik C, Mercimek-Andrews S. Creatine Deficiency Disorders: Phenotypes, Genotypes, Diagnosis, and Treatment outcomes. Turk Arch Pediatr., 2023;58(2):129-35.
• Buchberger W, Ferdig M. Improved highperformance liquid chromatographic determination of guanidino compounds by precolumn derivatization with ninhydrin and fluorescence detection. J Sep Sci., 2004 Nov;27(15-16):1309-12.
• Benoit R, Samir M, Boutin J, Samuel A, Brigitte C, Dominique D, Isabelle RV. LCMS/MS measurements of urinary guanidinoacetic acid and creatine: Method optimization by deleting derivatization step. Clin Chim Acta., 2019 Jun;493:148-155.
• Valongo C, Cardoso ML, Domingues P, Almeida L, Verhoeven N, Salomons G, Jakobs C, Vilarinho L. Age related reference values for urine creatine and guanidinoacetic acid concentration in children and adolescents by gas chromatography-mass spectrometry. Clin Chim Acta., 2004 Oct;348(1-2):155-61.
• Zinellu A, Sotgia S, Zinellu E, Chessa R, Deiana L, Carru C. Assay for the simultaneous determination of guanidinoacetic acid, creatinine and creatine in plasma and urine by capillary electrophoresis UV-detection. J Sep Sci., 2006 Mar;29(5):704-8.
• EURACHEM Guide 1998. The fitness for purpose of analytical methods: A laboratory guide to method validation and related topics. Available at http://eurachem.org/