Interference of Metamizol (Dipyrone) on the Determination of Creatinine with the Kodak Dry Chemistry Slide Comparison with the Enzymatic Method from Boehringer

Abstract

Summary:In order to eliminate positive interferences that take place with the Jaffe technique, the Kodak Ektachem and Boehringer Mannheim Companies have chosen an enzymatic method for the determination of creatinine in serum and urine. Pathological and clinical samples often contain metabolites in elevated concentrations or exogenous compounds such as drugs or toxic compounds. We noticed that patients receiving metamizol-containing drugs showed unusually low values of creatinine when determined with an Ektachem analyser. We investigated the effect of the main metabolites of this prodrug on the creatinine enzymatic methods of Kodak and Boehringer. We concluded that methyl-amino-antipyrine, the active substance after administration of metamizol (prop. INN) was responsible for the interference, and that no reliable determination of creatinine could be performed with these methods in the serum of patients receiving this drug.

Drug dosing using estimated glomerular filtration rate: Misclassification due to metamizole interference in a creatinine assay

“…These results suggest a negative interference by metamizole, corroborating other studies performed in vitro that have demonstrated that samples containing metamizole or its metabolites present with lower values for creatinine when determined enzymatically. 19 , 20…”

“…There are reports of the metamizole interference in the determination of other analysis by the same principle, being purposed an interaction in the peroxidase reaction. 19 Gascon-Roche and collaborators described a significant positive interference in the determination of free triiodothyronine (T3), cortisol, estradiol and a negative interference in the carcinoembryonic antigen, human chorionic gonadotropin and α-fetoprotein, when determined by an immunoenzymatic assay based in the luminescence that uses peroxidase as a marker. 27…”

“…Despite the meaningful advances, technological limitations are still present in the clinical laboratory routine, especially due to exogenous interfering substances, several drugs that can interfere with the series of enzyme-catalysed chemical reactions like metamizole. 19 , 20 Due to the risk of agranulocytosis, metamizole use has been banned in several countries such as the United States, Japan, Australia and recently India, 21 while it remains the first choice of non-opioid analgesic in many countries of the European Union and Latin America, including Mexico and Brazil, 21 and being the most prescribed analgesic drug in Germany. 22…”

Technical Note

“…Recently Bagnoud & Reymond(11) reported that patients receiving metamizol (Novalgin®, Litalgin®) 1 ), a widely used analgesic, had surprisingly low creatinine values, when measured with the dry slide enzymatic method of Kodak Ektachem (presently Vitros, Johnson & Johnson Clinical Diagnostics, Rochester, NY, USA). They showed clearly that methyl-amino-antipyrine, an active metabolite of the metamizol, interferes with the enzymatic tests of…”