The introduction of new LC systems or UPLC systems having reduced system volumes (i.e. low dwell and dispersion volumes), along with reduction of particle size of columns from 10 µm/5 µm to 3.5 µm and then to =1.8µm, led to improvement of the chromatographic performance w.r.t. sensitivity, speed and resolution.
To effectively leverage the power of smaller particles in narrow column formats while accelerating flow rate requires systems that operate at higher pressures and that are designed for both lower volumes and lower dispersion. The first design considerations involved the quality of tubing that could withstand UPLC operating conditions, so as not to dilute the magnitude gain in resolution brought about by UPLC column, hence extra-column volumes were minimized.
The UPLC pump delivers higher pressures, but retention time precision remains extremely important. The Waters UPLC system uses an automatic and continuous compressibility compensation algorithm that does not require user intervention to cope with these demands, resulting in retention time reproducibility. Also, electronically controlled pump-check valves ensure that the pump check valves close quickly, thus improving performance and priming reliability.
Since the introduction of binary pump UPLC about a decade ago and with the industrial success of UPLC-technology, we have now in market Quaternary pump UPLC’s & the UPLCs with further low dispersion volumes. The latest UPLCs can be used to run ballistic gradients that are gradient programmes even below 1 minute and chromatography columns of dimensions 1 mm can be used thus leading to faster developments and analysis. This throughput advancement has lead to increased implementation of UPLC in both Diagnostics and Research Labs also.
The implementation of UPLC has increased significantly in both Active Pharmaceutical Ingredient (API) and Formulation industries, in both their Research and Development centers (R&D’s) and Quality Control (Q.C.) Labs. The performance and savings (return on investment) associated while performing the typical tests such as reaction monitoring, assay, dissolution and related substances during the release and In-house testing by UPLC is significantly high. This saving in time in R&D centers further leads to faster product development that means products reach “early to market” and in Quality Control saving time during analysis leads to decrease in quarantine time of intermediates, faster release results for In-process testing and hence faster release of finished batches
The QbD approach as emphasized by US-FDA during analytical method development is an important reason for UPLC success in Pharmaceutical R&D’s, because of its capability to screen-n-scout the analytical methods much faster than the conventional HPLC. There is also a greater emphasis on future-proofing based procurement approach, where-in Quality control Labs and R&D centers have started budgeting and procuring latest UPLC’s which has capability to run conventional HPLC and UPLC analytical methods
The adoption of UPLC methods for various tests by different regulators like US-FDA, EMEA as release methods or alternative methods and adoption of UPLC by EP, USP in their monographs and medicinal compendia clearly reflects the reason for the increase in trend w.r.t implementation of UPLC technology in pharmaceutical industry.
(The author is Asst. Product Manager, Waters India Pvt Ltd, Bangalore)