They have been used since the 1960s and are considered the gold standard chromatographic method for amino acid analysis. The “Stein & Moore Method” published in 1958 laid the groundwork for this technique. They involve cation exchange chromatography to separate amino acids followed by post-column derivatization with ninhydrin and detection at 440nm and 570nm.They are recognized by regulatory bodies like the EU Commission as the reference method for amino acid analysis in food and feedstuff. They provide highly accurate and reproducible quantitative results for physiological fluids and are widely used in clinical settings to screen for inborn errors of metabolism in newborns. Though some alternative methods have been introduced over the past 25 years, classical analyzers remain unmatched in quantitative accuracy, ease of use, and low operating costs, keeping them the method of choice in many labs and hospitals globally. Their unique capabilities for detecting and quantifying specific amino acids make them critical for confirmation testing and avoiding missed diagnoses in metabolic screening of newborns.