Advances in Pharmaceutical Analysis

An introduction from the guest editors of this special supplement from LCGC Europe focusing on recent trends in pharmaceutical analysis.

The pharmaceutical industry is one of the most regulated industries worldwide because the drugs produced have to be safe and effective. To comply with the regulations and guidance of drug production and control, a wide range of analytical techniques have to be used. In this supplement from LCGC Europe, leading industrialists share their expertise in some of the most commonly used and promising separation-based techniques. Among them, gas chromatography (GC), two-dimensional liquid chromatography (2D-LC), supercritical fluid chromatography (SFC), and the hyphenation of chromatography with mass spectrometry (MS) can be cited. In addition, an interesting paper dealing with the use of LC–UV and LC–MS based process analytical technology (PAT) in the pharmaceutical industry is also featured.

The first article by Wenya Zhu and colleagues (from Novartis, China and Switzerland) describes a new way of using regular GC methods used for decades to determine residual solvents in pharmaceutical substances. In this work, the authors propose a LEAN approach where multiple solvents can be simultaneously determined based on predetermined relative response factors (RRF) against an internal standard with only one injection of sample solution. This allows laboratory efficiency and instrument utilization to be significantly improved (by about 60% compared to the conventional external standard-based methods).

Mass spectrometry has gained impetus in recent years and considering its potential, there is no doubt that it will be more and more widely implemented in more pharmaceutical laboratories in the coming years. Tony Bristow and Andrew Ray (AstraZeneca, UK) discuss the recent advances in MS hyphenated to chromatography and its application in pharmaceutical analysis. This includes the use of compact, easy-to-use mass spectrometers for simple applications based on well-established chromatography workflows; developments in SFC–MS; the increasing use of high resolution MS in combination with LC and GC; ion mobility-based techniques as orthogonal separation techniques; and the increasing need for MS for more demanding applications such as novel (larger) molecules and complex drug delivery systems.

Liquid chromatography is by far the most widely used separation method in the pharmaceutical R&D and quality assurance (QA) and QC laboratories. 2D-LC is a powerful approach offering novel solutions to problems ranging from complex samples requiring excessively large peak capacity to simple, yet difficult to resolve compounds. In his contribution, C.J. Venkatramani (Genentech, USA) illustrates the potential of 2D-LC in the modern-day pharmaceutical industry to address real problems covering a wide range of applications from coelution, to peak purity assessment, to simultaneous achiral-chiral analysis, to genotoxic impurities, and more.

Doug Richardson (Merck, USA) and Todd Maloney (Eli Lilly, USA) highlight the practical applications of online chromatography (also known as PAT) in pharmaceutical and biopharmaceutical process development and manufacturing. The increasing importance of PAT (using chromatographic approaches and hyphenated techniques) in pharmaceutical industry is emphasized and the current status and recent developments are illustrated through various industrial applications, including control in regulated continuous manufacturing.

Despite the fact that SFC was first introduced in 1962 by Klesper, it is still considered as a niche technique, mostly used for chiral separations and preparative scale applications in the pharmaceutical industry. However, the technique has recently seen a real metamorphosis and renewed interest for analytical achiral applications in the pharmaceutical analysis community. The contribution prepared by Claudio Brunelli (Pfizer, UK) describes the key achievements and strengths of modern SFC in the pharmaceutical industry. A particular focus is dedicated to the implementation of SFC in regulated quality control (QC) laboratories, including the state of the modern instrumentation.

As guest editors of this special issue, we would like to warmly acknowledge all authors for their excellent job, and we hope that these contributions will be of interest to the LCGC Europe readers.

Adrian Clarke Novartis Technical R&D, Basel, Switzerland

Davy Guillarme University of Geneva, University of Lausanne, Geneva, Switzerland