Mass Spectrometric Detector:

These are considered as the most sensitive detectors but there is a fundamental problem in coupling a liquid chromatograph with a mass spectrometer because of mismatch between the relatively large solvent volume and the vacuum requirements. Several interfaces have been developed for solving this problem as discussed later in Sec. 8.8 of this Unit.

An LC-MS instrument has three basics components: a liquid chromatograph, an interface and a mass spectrometer. In a commercial instrument, column is split with a tiny fraction introduced directly into the mass spectrometer. Direct liquid introduction systems are used in conjunction with the microbore column having typical flow rate in the range, 10 to 50 µ L/min. In another type of interface, the eluent is deposited on continuously moving belt/wire that transports the solvent and analyte to heated chamber for removal by volatilization. After evaporation of the solvent, analyte residue on the belt/wire passes into the ion source area where desorption-ionization occurs.

A new and promising interface called thermo spray has become available commercially and is useful in biochemical field. It permits direct introduction of the total effluent from a column at high flow rates of 2µ L/min. In this case, the liquid is vaporized as it passes through a heated capillary tube of stainless steel to form an aerosol jet of solvent and analyte molecules. The analyte in the spray is ionized through a charge exchange mechanism with a salt such as ammonium acetate incorporated in the eluent. Therefore, the thermospray is not only an interface but also an ionization source. Thus, this has the disadvantage of being applicable to polar analyte molecules and polar mobile phases that may dissolve ammonium acetate. Fourier transform mass spectrometers based on ion cyclotron resonance also hold immense potential for the analysis of thermospray produced ions. Thermospray interface provides spectra for a wide range of non-volatile and thermally stable compounds such as peptides and nucleotides with detection limits down to 1 to10 pg.