15
Figure 2. Novel small footprint high performance high mobility spectrometer - mass spectrometer Excellims MC3100.
chemical detection needs; the performance of the ambient pressure IMS systems are rarely improved upon. The recent development of a high performance IMS (HPIMS) system (Excellims Corporation, Acton, Massachusetts, USA) was an advance in small ambient pressure IMS systems, providing high resolving power, the capability for the rapid analysis of large organic molecules and biologics from a liquid sample (vs. volatile/semi-volatile small molecules only for conventional IMS), as well as a broader linear response range. In principle, IMS can deliver chromatography- like separation in the gas phase. One can consider it as gas phase electrophoresis. When an ionised sample mixture travels in the drift gas, in contrast to condensed phase media, a typical ion mobility separation can be achieved within 50 milliseconds with an average peak width (FWHM) of 180 microseconds.
Recent HPIMS developments have demonstrated ion mobility-based separation can deliver resolving power that is comparable to HPLC [4]. With added electrospray ionisation (ESI) capability, ESI-HPIMS is poised be an alternative separation method to HPLC, especially in those applications where fast analysis is required at the point of origin. HPIMS inherited many unique features from the conventional IMS system, including its independence of operating environments; its high temperature operation conditions, which reduce carry over and contamination; and the little or no consumption of organic solvents which makes it much cheaper to operate.
Many examples of HPIMS applications can be found in the pharmaceutical process analytical technology (PAT) area where HPLC has been the most reliable workhorse for decades. However, typically the HPLC is set up in a lab environment and takes minutes to tens of minutes per sample. With a
rapid measurement-to-result time, HPIMS analysis only takes a few seconds and can be performed at-line, in-line or on-line in the manufacturing process. PAT applications may include reaction monitoring [5], dissolution studies, and cleaning validation in chemical and pharmaceutical manufacturing processes. IMS for cleaning validation has been well developed and adopted [6]. With HPIMS, superior analytical performance and the capability of analysing non-volatile Active Pharmaceutical Ingredients (API)s, excipients, and detergents become a reality. It can be set up in a lab with automation, or at line for a quick screening for contamination. For example, a typical cleaning validation procedure involves 50+ samples; if a typical HPLC analysis for this procedure takes 12 minutes, it will take 10 hours to complete the validation. With a typical <1 minute per sample analysis time, the HPIMS may complete the analysis within one hour. Another attractive feature of the HPIMS is that it eliminates the usage of large amounts
of solvents. Compared to HPLC, it is a green analytical technology with savings in running and waste disposal costs.
With the abundance of isomeric structures and lack of chromophores, sugar analysis has posed significant challenges to current HPLC methods. Refractive index detection for HPLC has poor sensitivity compared to UV and requires longer run times. Figure 1 shows the ESI-HPIMS ion mobility spectra of the isomers melezitose and raffinose. The x-axis is measured drift time and y-axis is the intensity. Typical resolving power (R = td
/t1/2 , where td is the drift time and t1/2
is the full width at half maximum for the peak) of the HPIMS is at 70 to 100. In this example, isomers melezitose and raffinose are baseline separated based on their ion mobility, while the measured resolving power is about 80, approximately 35,456 theoretical plates. HPIMS could be an ideal sugar analyser offering superior resolving power and analysis speed in seconds [7].
Figure 3. Mass spectrum of Venlafaxine obtained on HPIMS-MS.
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