Faster UHPLC systems offer solutions with added benefits.
Pharmaceutical companies, like other industries, face frequent and mounting requirements to resolve complex mixtures of active pharmaceutical ingredients into their unique components. Given the demands being placed on medicinal chemistry departments to deliver high-quality new drug candidates, the speed at which separations can be achieved is of utmost importance. Yet, despite the industry’s best efforts to reduce turnaround times by increasing instrument resources, the wait for results has sometimes approached an hour. Moreover, an increase in instrument resources isn’t always a viable option due to space limitations and budget constraints.
Medicinal chemistry laboratories have historically relied on a number of different high-performance liquid chromatography/mass spectrometry (HPLC/MS) systems in an open-access environment to provide synthetic chemists with oftentimes critical information about the success of their reactions and processes. To access such information, the medicinal chemist typically walks up to one of several open-access systems configured for this purpose, submits a sample to the queue and selects a protocol HPLC/MS method. Data are generated, circulated and automatically stored. Under current equipment and column technologies the average run time for existing HPLC methods is six minutes, inject to inject.
This time frame can be problematic. In any given working environment, existing systems will begin to reach capacity quickly for daytime activities; and it’s normal practice to observe slight variability of data between individual instruments, which will only add to the administrative burden.
But with modern systems able to offer significantly improved peak capacities, the evaluation of ultra HPLC (UHPLC) technologies as an approach to delivering a high-capacity, robust, open-access solution presents a compelling alternative. After careful evaluation of the instrumentation and the development of complementary methods to existing, local HPLC, routines that achieved equal or improved data quality in less than 2.5 min were delivered. The immediate impact of this approach has been to more than double the instrument capacity, while reducing costs by lowering solvent consumption and associated waste-disposal costs. The ability to schedule overnight analysis on a selection of screening columns has led to improved time management and planning, in addition to analyzing multiple array samples without impacting the daytime laboratory analyses.
A key benefit achieved by the new instrumentation has been improved data reproducibility across instrument platforms and the ability to perform fully automated QC and instrument performance checks. This is key. When medicinal chemists are tracking a specific reaction, any shift in retention time from one analysis to the other can suggest something unintentional has occurred during the reaction or process. As any medicinal chemist will tell you, this can lead to significant delays.
The capacity for analysis, realized upon deployment of the new instrument platforms, has ensured that identical results can now be achieved independent of whichever instrument has been used to perform the analysis. This, in turn, has helped to “smooth” instrument queue times, as there’s no longer a tendency for particular instrument configurations to produce enhanced data quality over others, and thus be favored by multiple users. Deciding which instrument to use has switched focus to queue length and proximity to the user, rather than data quality.
This approach has been further enhanced by the improvement in software stability and functionality. A simple graphical user interface allows end users to interpret their results and achieve reliable integration of chromatograms, without the need to be trained in complicated bespoke software packages. Data can be sent directly to desktops in an easy-to-understand format, alleviating a key concern driving productivity in the chemistry laboratory.
The new instrument platforms can also be easily configured to allow both column and solvent switching in an open-access environment. Through a combination of diversity-of-stationary phase selectivity, mobile phase solvent selectivity and multi pH mode screening, users now have automated access to explore a wide space quickly and easily.
Indeed, their ease-of-access and throughput speed allows the system to be used as a first pass screen for all samples submitted to the purification group. The development and adoption of “calibrated” preparative methods, using data supplied by the UHPLC instrumentation, provide further reduction of non-value-added processes. This then negates the requirement for preparative-scale method scouting, with associated savings in both time and solvent. To sum up, the installation of new UHPLC instrumentation has provided a state-of-the- art replacement for aging HPLC instruments and reduced both consumable and laboratory space requirements, while allowing the refinement of both analytical and purification processes.
And the ultimate payoff? Increased laboratory productivity.