text: Before Jaffe, Neubauer described a similar precipitation reaction by mixing creatinine with zinc chloride (ZnCl) and performing a Weyls test—the addition of SNP to NaOH and then incubating with acetic acid (CHCOH) to develop a color change. Until Folin developed Jaffes reaction into a clinical procedure, Neubauers method was how creatinine was measured. As Folins method evolved, various techniques were implemented to remove Jaffe-reacting substances, mostly protein, from the sample and increase specificity. By the 1950s, precipitated aluminum silicate, called Lloyds reagent, was being used to remove protein from serum, further improving accuracy. Fullers earth was also used for protein-binding, but the reference method until the 1980s was adsorption with Lloyd's reagent. New concerns arose due to non-standardization of procedures; different labs were reading results at different endpoints. This problem was resolved with the advent of automated analyzers in the 1960s and 1970s, which introduced a kinetic reading of results rather than a specific endpoint. Kinetic Jaffe methods involve mixing serum with alkaline picrate and reading the rate of change in absorption spectrophotometrically at 520 nm. This not only standardized the procedure, but also removed the need for sample deproteinization. It also introduced two new problems—analyzers used an algorithmic compensation to correct for pseudochromogens, and calibrations were not yet standardized between instruments.
  The 1980s saw several new technologies that promised to change the way creatinine testing was done. Enzymatic and ion-exchange methods provided better accuracy but had other drawbacks. Enzymatic methods reduced some interferences but other new ones were discovered. High-performance liquid chromatography, HPLC, was more sensitive and specific, and had become the new reference method endorsed by the American Association for Clinical Chemistry. HPLC addressed the shortcomings of Jaffe-based methods, but was labor-intensive, expensive, and therefore impractical for routine analysis of the most frequently ordered renal analyte in medical labs. Simple, easily automated and cost-effective, Jaffe-based methods have persisted into the 21st century, despite their imperfections.
  By 2006, isotope dilution mass spectrometry (IDMS) became the reference method. To improve the accuracy in creatinine testing, new standards were developed by the National Institute of Standards and Technology (NIST). The College of American Pathologists (CAP) and  the National Kidney Disease Education Program (NKDEP) collaborated with NIST to develop a new control reference called standard reference material 967 (SRM 967). SRM 967 aims to standardize calibration of creatinine testing, including Jaffe methods. Use of both IDMS and SRM 967 are currently recommended by the National Institutes of Health.