Problem: Detecting impurities in any chemical reaction has always been important to the chemist and it is becoming increasingly important to detect those present at low levels, (e.g. 0.5%).
Common methods of assessing purity include chromatography with a detector, such as an ultraviolet light detector (UV) or an evaporative light scattering detector (ELSD). However, these detectors do not give any information about the molecular weight or structure of the impurities detected and thus makes identification difficult. A complimentary detector which can be used with a chromatograph is the mass spectrometer. Various types are available, but their size, initial purchase and subsequent running costs can often make conventional mass spectrometers prohibitive for use in everyday laboratories.
These historical barriers of conventional mass spectrometer design can result in compromises having to be made in the choice of chromatography. This can result in a chemist having to select a less effective detector for their application needs which can create unnecessary work-flow.
Solution: Recent technological advancements have seen the development of a miniature mass spectrometer. Micro- Electro-Mechanical Systems or MEMS have allowed successful miniaturization of the components found in a conventional mass spectrometer. The result is a very powerful technique available to many more users and applications and provides chemists with an efficient and effective detection method of impurities in chemical reactions.
An experiment was conducted to highlight how a miniature mass spectrometer can be used as an HPLC detector to identify the presence of impurities that would otherwise be lost using popular detection methods. A miniature mass spectrometer (Microsaic MiD®) was attached to an HPLC using its SFI (Split Flow Interface), which contains a passive split and the spraychip® ESI source. Contact closure triggering from the HPLC and the analogue output from the UV detector were connected to the instrument, allowing it to be run automatically from the HPLC and to capture the UV data. Two test samples were used containing well resolved compounds: Bromopride, Verapamil and Cortisone.
The instrument confirmed the presence of each compound, demonstrating that a miniature mass spectrometer can be coupled to an HPLC system to extend the capability to LCMS. This added functionality allows medicinal chemists to identify unknown impurities in samples down to the low level of 0.5% using full scanning mode. Sometimes impurities co-elute with the main analyte and thus cannot be observed using a UV detector. In the case of co-elution on the HPLC system, the miniature mass spectrometer will indicate and identify an impurity where the UV data would provide misleading results.
The system is portable and fully self-contained, including PC and all pumps in a unit the size of a conventional UV detector. It can be easily integrated into a wide range of bench-top applications. Using MEMS technology allows for ‘plug and play’ solutions for routine maintenance, negating the need for costly service contracts. The benefits of miniature mass spectrometry efficiently overcome bench space availability, noise and vibration, heat generation and laborious workflows.
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