New Levels of Sensitivity in LC-MS

Liquid chromatography-mass spectrometry (LC-MS) is an analytical technique commonly used in a vast number of fields. For many of its applications, sensitivity in LC-MS is of paramount importance.  

SCIEX has developed its most sensitive LC-MS system to date: the SCIEX 7500 system. Technology Networks spoke to Jack Steed, a technical specialist from SCIEX, about the latest software and hardware developments related to this system and applications that could benefit.

Katie Brighton (KB): What are some common applications of LC-MS?

Jack Steed (JS): The use of LC-MS varies widely with its adoption across numerous markets and for a vast array of applications. Typically, its use splits into the following categories: pharma, biopharma, clinical, forensic, food, environmental, industrial and life science research.

Within these categories, there are many key applications that are relevant to the individual fields, from the creation and safety testing of new pharmaceuticals to testing contaminants within rivers and the food we eat every day. In addition, LC-MS is used to screen newborns and test for drugs of abuse. The scope for LC-MS is vast and its use has proliferated over the years to become one of the most widely used and trusted analytical techniques.

KB: What challenges do scientists using LC-MS face? How are these challenges addressed by the SCIEX 7500 system?

JS: The main challenge when using LC-MS is the different matrices that are being analyzed. Many researchers strive to reduce sample preparation as much as possible while minimizing matrix effects, shortening the time spent on complex clean-up steps and decreasing associated errors and costs. However, when analyzing a complex sample, it is paramount to ensure that the sample is as “clean” as possible to lessen matrix effects and make sure that the analytes of interest are not negatively affected by the other components within the sample.

This is where the sensitivity of the SCIEX 7500 system comes in. This system is the most sensitive instrument SCIEX currently provides, and it allows for the simple use of dilution in sample preparation and lowered injection volumes to reduce matrix effects. With our previous instruments, you may have needed to use a 10 µL injection volume. With the SCIEX 7500 system, you may only need a 1 µL injection volume, or you may be able to dilute your samples 10 times, which helps minimize matrix effects and reduce sample preparation. This also decreases ion suppression, which is a major barrier to a successful analysis. This suppression occurs when analyzing complex samples that have not been sufficiently “cleaned up” due to multiple components being within the source of the mass spectrometer at any one time. This can “use up” the available charge and lead to a reduction in signal when compared to your external standards.

KB: Can you talk us through some of the features of the SCIEX 7500 system and how they provide benefits to the user?

JS: Three main aspects separate the SCIEX 7500 system from our previous generation of instruments: new software, ion optics and source.

The main hardware improvements and updates of the SCIEX 7500 system combine to provide an industry-leading level of sensitivity, with this improvement being achieved in two main ways. First, the innovation of the D Jet ion guide has allowed for an increased volume of ions to be sampled by the instrument and has facilitated an increased orifice size. This allows for a larger volume of ions to be introduced that can then be detected, therefore increasing sensitivity. The other main innovation is the OptiFlow Pro ion source, which is a new source and is solely provided for the SCIEX 7500 system. The reason for this change was to allow for the easy interchange and use of different flow rates, from 1 µL/min to 3 mL/min, and to incorporate into the system the E Lens probe, which is another way we have been able to improve the sensitivity of the system. The E Lens probe is a charged electrode that is introduced into the middle of the source and, in effect, drives ions toward the orifice and improves droplet breakup, which also improves the sensitivity of the system.

Outside of hardware, the new software is SCIEX OS software, which over the last few years has revolutionized our software offerings and has brought mass spectrometry software into the 21st century. The SCIEX 7500 system was our first nominal mass instrument to be fully integrated into the new platform, and this was an important step in the long-term integration of the software across all our instruments. In terms of the benefits SCIEX OS software provides, the software was created with usability in mind, with the thought that new users should feel comfortable from the minute they see the homepage. This has been achieved using a tile design that will be familiar to almost anyone and by providing an easy-to-navigate workflow and a low barrier to use. In addition to usability, regulatory compliance was built into the software from the start, in contrast to older software, where compliance was added later due to relatively recent changes and the necessities of working in a compliant laboratory.

KB: What changes can be made to the sample preparation workflow when using the SCIEX 7500 system?

JS: While this question is partly covered in my previous responses, it is worth reiterating the sample preparation workflow changes that are enabled by the SCIEX 7500 system. Essentially, the increase in the sensitivity of the system allows for an increase in sample dilution and the possible removal of some of the more costly and time-consuming aspects of sample preparation, such as solid phase extraction cleanup. This enables an increase in sensitivity that can lead to time savings and reduced costs during sample preparation. An increase in sample dilution can also be performed, meaning that fewer matrix effects will be observed and the system will maintain its performance over a longer period of time.

KB: What applications do you think benefit most from this platform?

JS: The main applications that can benefit from the SCIEX 7500 system are methods where sensitivity is of the utmost importance. These include a vast range of different workflows, such as the analysis of low-dosage drugs (for example, fluticasone propionate, which is an anti-asthmatic medication), where the circulating levels within the blood are very low. Another example would be drinking water testing, where levels required by regulators continue to decrease to help ensure that the health of people is not impacted simply by the water they drink. In addition, due to sensitivity being a driver in most applications, almost any method can be improved by this increase in sensitivity, whether by increasing sample dilution or achieving low limits of quantification.

KB: What software is available to support scientists using the SCIEX 7500 system?

JS: As I mentioned previously, one of the main drivers of the SCIEX 7500 system is the adoption of SCIEX OS software for both acquisition and data processing, with the transition from our previous Analyst software now coming to fruition. In terms of add-ons to the software, we also have several compound libraries across multiple markets and applications. These include libraries for drugs of abuse, per- and polyfluoroalkyl substances, natural products, extractables and leachables and many more that can be implemented within SCIEX OS software and used to help with compound identification and confirmation.

Jack Steed was speaking to Katie Brighton, Scientific Copywriter for Technology Networks.