HPLC–ELSD is a simple, robust technique. It is especially useful for analytes without significant chromophores, or with mobile phases that have UV chromophores (43,51,79). It also has been used as a surrogate mass spectrometry (MS) detector during method development, albeit with lower sensitivity. It is a mass flow sensitive detection method — it responds to larger amounts (quantities) of analytes, and it gives a larger relative response the larger the amount or mass of the analyte passing through the detector — rather than a concentration detection method, as is UV detection. Quantitative HPLC–ELSD has been used recently to study analytes from dried leeches (44), fungi (13), and medicinal plants (7,14–16,18,22,26,27,29,45,48,49,88–92), human intestinal (28) and bronchoalveolar (2) fluids and human breast milk (72), as well as blood (12,57), bile acids (24), underivatized amino acids (44,62), sugars (46,75), lipids (4,9,12,19,24,28,50,55,56,72,76,79), foods (3,4,50,55–56,76,79–87), antibiotics (17,25,54,63–68), pharmaceutical excipients (9,11,20,21,47,58,70), surfactants (73), detergents (74), nutritional supplements (19,30,61), polymers (6,69), and many "traditional" pharmaceutical compounds (1,53,57,77). However, it has been unsuccessful with some combinatorial chemical libraries (5,8,36) to date. As a vote of confidence in quantitative ELSD, in 2006, NIST (30) published two cross-validated quantitative HPLC methods (LC–MS and HPLC–ELSD with isocratic elution) for the analysis of its Standard Reference Material 3280, Biotin. Although the LC–MS method was far superior in terms of quantitative sensitivity (LOD, LOQ), both methods produced similar quantitative results. NIST concluded that either method alone could be used potentially as a reference method for the quantification of biotin in multivitamin tablets.