Non-volatile buffers such as phosphate and citrate are generally incompatible with mass spectrometric detection (LC-MS) or cause significant interference with ion generation. In the case of conventional HPLC flow rates, continuous deposition of buffer causes fouling of the mass spectrometer ion source it may degrade the performance of the LC/MS interface.
LC-MS (Liquid chromatography-mass spectrometry) is an analytical technique in chemistry that combines the physical separation abilities of LC with the capabilities of MS. The high-performance liquid chromatography separates the sample mixtures of molecules and mass spectrometry gives structural identification of each molecule with high detection sensitivity and molecular specificity.
It is suggested that the phosphate buffer should avoid in the mobile phase of LC-MS analysis due to their low volatility. A huge amount of buffers passed in ESI that are complicated to eliminate and large amounts of salt is formed in MS. This is the main reason to avoid this type of buffer. If your analyte contains a phosphate group, this is not the issue, because we use the analyte concentration in nanograms. You can use trifluoroacetic acid (TFA) as an alternative to the buffer as it is acidic and volatile.
The mobile phase must be volatile when a mass spectrometer is used as a liquid chromatography detector, as one of the functions of the LC-MS interface is to vaporize the mobile phase. The main problem is that the phosphate buffer is non-volatile and so cannot be used in LC-MS experiments.
There are limited buffer options available for LC-MS because the buffer must be volatile in LC-MS applications. The most common LC-MS buffers are acetate, formate, ammonia, and bicarbonate, etc. Analysis of analytes in the pH 2.0 to 3.8 and pH 5.8 to 8.0 ranges are typically performed with ammonium acetate. Analysis of analytes in the pH 2.7 to 3.7 ranges are typically performed with ammonium formate. Analysis of compounds in the pH 6.6 to 8.6 ranges are typically performed with ammonium bicarbonate. These are not completely cover the required buffering range but are the only option for LC-MS applications.
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