Jaap de Zeeuw and Jana Hepner describe how a new column solution makes the speed benefits of LPGC-MS widely attainable
Using a mass spectrometer as a gas chromatography (GC) detection system has many advantages when it comes to compound identification and quantification, but there is another less known opportunity: speeding up analyses by using the mass spectrometer (MS) vacuum to lower pressure within the column. This technique is known as “vacuum-outlet GC,” or “low-pressure GC-MS” (LPGC-MS), and it can provide significant gains for fast GC-MS. As shown in Fig. 1., LPGC-MS using an LPGC column kit was three times faster than a conventional GC-MS analysis of multiresidue pesticides in food. The column kit overcomes hurdles that have traditionally been a barrier to LPGC adoption, making it simpler to set up for this technique and take advantage of the significant speed gains that it offers.
Why use LPGC-MS for fast GC-MS?
What makes LPGC-MS a favourable choice among the options for fast GC-MS? For MS work, 30m x 0.25mm ID columns are typically used. This format generates about 120,000 theoretical plates; has optimum carrier gas flow rates within the MS vacuum pump capabilities; and can maintain positive inlet pressure, despite the vacuum at the end of the column. There are several ways to increase the analysis speed of a flow-optimised 30m, 0.25mm ID column; the following is how they compare to the LPGC-MS approach used in Fig. 1.
Use a shorter, narrower column. A 10m x 0.10mm column will provide similar efficiency (plate number) and resolving power to a 30m x 0.25mm column. However, this format has very low column capacity, requiring very low concentrations or injection volumes to avoid peak distortions.
Use the 30m x 0.25mm column in the MS at a higher flow. Increasing flow is easiest way to reduce analysis time. But, to get a 3x faster analysis time, a flow of approximately 12 mL/min is needed, which requires an inlet pressure of approximately 63 psi. This is problematic for injection, MS data acquisition rate, and MS pump capacity.
Use a 10m x 0.25mm column at optimal carrier gas flow rate. A 3x shorter column has about 40,000 theoretical plates and should give 3-4x faster analysis time, but the inlet pressure required for this column is about 0.35psi, which is very difficult to control. At such pressures, split injection is a challenge, column trimming is hardly possible as it impacts pressure, and MS data acquisition can be difficult due to very narrow peak widths.
Use an LPGC column kit. An LPGC column kit consists of a 15m x 0.53mm analytical column that is factory coupled to a 5m x 0.18mm restrictor column. This configuration produces about 30,000 theoretical plates and can be operated at standard flow rates of around 2mL/min. Because of the vacuum inside the 0.53mm ID analytical column, optimal carrier gas linear velocities are very high, resulting in very short analysis times (typically 3x faster than for a 30m x 0.25mm column). Peak widths are 1.5-2 seconds, which is broad enough for sufficient MS data acquisition. Additionally, 0.53mm columns have high capacity due to the 1 µm Rtx-5ms film.
How it works
LPGC-MS works by using the MS vacuum system, along with a specially designed column setup, to lower pressure inside the entire column, thereby significantly speeding up analysis. As shown in Fig. 2, by using a 0.53mm analytical column that is inserted directly into the MS and a flow restrictor on the GC inlet side, low pressure can be maintained throughout a 0.53 mm analytical column. The reason an LPGC column kit makes this technique easier is because it provides a robust, zero-dead-volume, factory coupling of the necessary restrictor column and the recommended analytical column, which also includes an integrated transfer line. The LPGC column kit has been specifically designed to install easily, and each one is tested to ensure leak-free performance, meaning the setup for LPGC-MS can now be as simple as changing a column.
Even though the LPGC column kit makes the technique’s physical setup much simpler and more reliable than making manual connections, some method development time is still required when translating a conventional method. This includes setting the column dimensions (restrictor column only) in the GC software and adjusting the oven ramp and flow rate as necessary. Online method translation calculators should not be used because they do not allow you to directly calculate new method conditions for low-pressure GC. Although some method development work will be necessary when implementing LPGC, the significant increase in sample throughput makes it a worthwhile investment.
1. S.J. Lehotay, J. de Zeeuw, Y. Sapozhnikova, N. Michlig, J. Rousova Hepner, J.D. Konschnik, LCGC North Am. 38, 457–466 (2020).]
Jaap de Zeeuw and Jana Hepner are with Restek