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Abstract
The reaction of picric acid (2,4,6-trinitrophenol) with creatinine under strongly alkaline conditions, originally described by Jaffe >100 years ago (1), remains the most common means of measuring creatinine in clinical samples. However, picric acid reacts with many compounds besides creatinine to yield colored products (1)(2)(3)(4)(5). Ketones, glucose, proteins, cephalosporins, and other compounds react to yield positive interferences; also, decreases in the color of bilirubin and hemoglobin under the reaction conditions yield negative interferences (2)(3)(4)(5)(6)(7). To counter these interferences, analysts have tried many variations of the Jaffe reaction, including modifications of sample preparation, addition of oxidizers to remove interferents, solvent extraction of interferents, pH adjustment of the reaction, continuous-flow dialysis, and kinetic measurement of the reaction (2)(3)(4)(5). In kinetic methods, the most common approach to decreasing interferences, the timing of the absorbance readings can be selected to minimize the effects of components that react faster or more slowly than creatinine. For most samples, these modifications of the alkaline–picric acid methods have improved the specificity of measurement. Results have become closer to the “true” creatinine values determined with reference methods (2)(3)(4)(5)—improvements in measurement that have led to a downward adjustment of creatinine reference intervals by ∼3 mg/L (8)(9) (to express creatinine in μmol/L, multiply mg/L by 8.84).

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