The role of the detectors in High-Performance Liquid Chromatography (HPLC) is to analyze the solutes as they exit from the chromatographic column. The detector recognizes the solute's property and generates corresponding electrical signals, which are converted into a readable graph of the detector's response versus elution time called a chromatogram at the computer. There are several types of HPLC detectors, each with its own advantages and limitations, depending on the analyte properties and the required sensitivity. It's important to note that no single HPLC detection method can detect all analytes. For this reason, HPLC systems may incorporate two or more detectors in the same run to enhance detection accuracy and sensitivity. Some commonly used HPLC detectors include spectrophotometric detectors, refractive-index detectors, electrochemical detectors, mass spectrometry detectors, Fourier-transform infrared (FTIR) detectors, light scattering, and photoionization detectors.

UV-visible (UVD) and fluorescence detectors (FLD) are spectrophotometric detectors. UV-visible detectors measure the amount of light absorbed by the analyte at a specific wavelength in the presence of a non-absorbing mobile phase. They are widely used because they are simple, reliable, and provide good sensitivity. They are most effective for detecting compounds with aromatic or conjugated double-bond systems. Fluorescence detectors measure the fluorescence emitted by the analyte when excited by light of a specific wavelength. They are highly sensitive and selective, making them suitable for detecting compounds with fluorescent properties. They are commonly used for the analysis of pharmaceuticals, environmental pollutants, petroleum products, and natural products.

Refractive-index detectors (RID) measure the difference in refractive index between the mobile phase and the analyte as it passes through the detector. They respond to almost all solutes, but they have some drawbacks. They are sensitive to changes in pressure and temperature, have low sensitivity, and can not detect trace analytes. They are commonly used for the analysis of non-chromophoric and non-fluorescent compounds, such as sugars, lipids, and polymers.

Electrochemical detectors (ECD) measure the electrical properties of the analyte, such as its oxidation or reduction potential. These detectors are based on amperometry, voltammetry, coulometry, and conductometry. They are commonly used for the analysis of compounds that can be electrochemically active, such as neurotransmitters, amino acids, and pesticides.

Mass spectrometry (MS) detectors identify and quantify analytes based on their mass-to-charge ratio. They are highly sensitive and specific, making them suitable for detecting trace amounts of analytes. The problem with these detectors is that they require gas-phase samples, and the solvent must be vaporized. Mass spectrometers are commonly used for the analysis of complex mixtures, such as proteins, peptides, and metabolites. Other detectors include FTIR, light scattering, and photoionization detectors.