1. PERFORMANCE IN ERNDIM SPECIAL ASSAYS FOR CREATININE DISORDERS Alberto Burlina & Cas Weykamp

2. Clinica Chimica Acta 361 (2005) 1 –9 creatinine

3. ERNDIM Special Assay Schemes: Analytes 2007 Urine 5-OH-Indolacetic acid Carnitine free CreatineCreatinineGuanidinoacetate Homovanillic acid Hydroxyproline Lactic acid Mucopolysaccharides Orotic acid Pipecolic acid Sialic acid Succinylacetone Uric acid Serum 3-OH Butyric acid 7-Dehydrocholesterol Aceto acetate C22:0 Behenic acid C24:0 Lignoceric acid C26:0 Cerotic acid Carnitine free Creatine Guanidin acetic acid GalactoseHomocysteine Lactic acid Phytanic acid Pipecolic acid Pyruvic acid

5. S-Guanidinoacetate (17%) MetodsN°Lab% GC/MS (with stable isotope dilution) 519,2 GC13,8 LC-MS/MS1350,0 LC/MS415,4 GC/MS27,7 HPLC13,8

6. S-Creatine (19%) MetodsN°Lab% GC/MS (with stable isotope dilution) 517,2 GC26,9 LC-MS/MS1344,8 LC/MS413,8 GC/MS26,9 HPLC13,4 Other26,9

8. U-Creatinine (70%) MetodsN°Lab% Jaffé end-point2426,7 Jaffé Kinetic2426,7 Hitachi1516,7 Dry Chemistry1516,7 HPLC22,2 LC-MS/MS33,3 Other77,8

9. U-Creatine (24%) MetodsN°Lab% GC/MS (with stable isotope dilution) 514,3 GC12,85 LC-MS/MS1851,4 LC/MS38,6 GC/MS617,1 HPLC25,7

10. U-Guanidinoacetate (26%) MetodsN°Lab% GC/MS (with stable isotope dilution) 615,4 LC-MS/MS1846,2 GC/MS820,5 HPLC37,7 Other410,3

11. Methodology and Quality Assurance in IEM Principles Parameters for method validation (details: ERNDIM web-site, http://www. erndimqa.nl)  Specificity  Selectivity  Precision  Repeatability  Reproducibility  Accuracy  Recovery  Range  Linearity  Limit of detection  Limit of quantitation

12. Special assays serum 2007 CreatineGuanidinoacetate Accuracy (Mean) 68,712,2 Precision (CV% Duplicates) 7,1%8,4% Linearity ( r )0,98340,9935 Recovery (%added analyte) 100%112% N° Lab.3330 Inter Lab CV12%15,2%

13. Special assays urine 2007 CreatineCreatinineGuanidinoacetate Accuracy (Mean) 3297,77116 Precision (CV% Duplicates) 8,8%3,4%6,1% Linearity ( r )0,99270,99770,9865 Recovery (%added analyte) 116%104%107% N° Lab.4310046 Inter Lab CV27%5,7%14,9%

14. Special Assays a. Remove of hydroxyproline b. Low level mevalonate c. Low levels carnitine d. Low levels 3-hydroxybutyrate, urate and creatine PROPOSAL