Pharmaceutical Analysis

In the pharmaceutical industry, method validation is essential. But what are the best practices? We review regulatory requirements, validation parameters, methodologies, acceptance criteria, trends, and software tools.

Here we provide an overview of the fundamentals and best practices on the development of stability-indicating HPLC methods for drug substances and products. We explain both traditional and easier modern approaches to developing stability-indicating HPLC methods—including using a universal generic method for new chemical entities—and address regulatory considerations and life cycle management strategies.

Determining product shelf life is a regulatory requirement for pharmaceuticals and many other regulated consumer products. In this comprehensive overview of stability studies and testing, we summarize current regulatory requirements, share industry practices for forced degradation, and explain approaches for reduced testing and data evaluation to expedite stability study timelines.

A fast ultrahigh-pressure liquid chromatography (UHPLC) method, with low solvent consumption, is described for the determination of coenzyme Q10 in a variety of complex formulations. This method exhibits good linearity, reproducibility, accuracy, recovery, and specificity, while resulting in an acceptable limit of detection (LOD) and limit of quantification (LOQ).

This article will discuss the benefits of 2D-LC and multiple application areas in (bio)pharmaceutical analysis, and will highlight the challenges and future outlook.

This article presents possible uses of ion chromatography and related techniques combined with various detection methods for clinical and pharmaceutical analysis of common inorganic and organic anions and cations. An overview of achievements in this area from the past 10 years is presented and the most important trends and development perspectives for ion chromatography are described.

The main objective of this review article is to provide a clear summary of the different methods that can be used to quantify endogenous small molecules. Because of the increased use of mass spectrometry (MS) in the field of bioanalysis, a special focus will be placed on quantification by liquid chromatography (LC)–MS. Practical recommendations to face this bioanalytical challenge, in particular in terms of method validation, will also be provided.

The main objective of this review article is to provide a clear summary of the different methods that can be used to quantify endogenous small molecules. Because of the increased use of mass spectrometry (MS) in the field of bioanalysis, a special focus will be placed on quantification by liquid chromatography (LC)–MS. Practical recommendations to face this bioanalytical challenge, in particular in terms of method validation, will also be provided.

The European Pharmacopoeia (Ph. Eur.) defi nes requirements for the qualitative and quantitative composition of medicines, as well as the tests to be carried out on medicines and on substances and materials used in their production.

This article focuses on ways to accelerate glycan screening data analysis, while keeping high reproducibility.A major focus of the pharmaceutical industry is the production and development of biologics-therapeutics produced via biological means-to provide novel treatments for diseases with unmet clinical needs. A large percentage of biologics under development are proteins, such as monoclonal antibodies (mAbs), fusion proteins, antibody–drug conjugates (ADCs), and enzymes. The structures of these protein drugs are made more complex by post‑translational modifications (PTMs).

For your highly sensitive UHPLC–MS analyses, how can you reduce noise and additional signals to a minimum?

Here we applied our newly developed UHPLC C18 and C30 columns to oligonucleotide analysis.

In this application, a simple method to simultaneously analyze various water-soluble vitamins was developed.

This review article will give a general overview of the liquid chromatographic (LC) and gas chromatographic (GC) methods used by analytical laboratories for the detection and characterization of suspected illegal medicines and health products, including lifesaving drugs (antimicrobials and antimalarials), lifestyle drugs (erectile dysfunction drugs), and biotechnology drugs (doping peptides and skin-tanning peptides). Literature published from 2015 until early 2019 will be surveyed.

LCGC Europe spoke to Yong Liu and Adam Socia from MSD about the cost-saving benefits of implementing green chromatography in the pharmaceutical sector, the importance of analytical method volume intensity (AMVI), and effective practices to reduce solvent consumption and replace harmful solvents, including supercritical fluid chromatography (SFC), fast chromatography, and “cocktail chromatography”.

This review article will give a general overview of the liquid chromatographic (LC) and gas chromatographic (GC) methods used by analytical laboratories for the detection and characterization of suspected illegal medicines and health products, including lifesaving drugs (antimicrobials and antimalarials), lifestyle drugs (erectile dysfunction drugs), and biotechnology drugs (doping peptides and skin-tanning peptides). Literature published from 2015 until early 2019 will be surveyed.

This article reviews the changing role of mass spectrometry (MS) hyphenated to reversed-phase liquid chromatography (LC) and alternative separation techniques in late-stage pharmaceutical development. The impact of the changing portfolios within the pharmaceutical industry is discussed as the industry moves from a traditional small-molecule model to a more diverse portfolio. A new generation of high‑resolution mass spectrometers and ion mobility mass spectrometers operating as orthogonal separation techniques has greatly increased the ability to resolve impurities and increase the level of knowledge gained from a single experiment. The continued impact and innovation of gas chromatographyÐmass spectrometry (GCÐMS) in late-stage development is also discussed.

The evolution of two-dimensional liquid chromatography (2D-LC) instruments along with improved software capabilities has transferred 2D-LC from the hands of experienced researchers to functioning analytical laboratories in the pharmaceutical industry. 2D-LC offers chromatographers novel solutions to problems ranging from analyzing complex samples requiring excessively large peak capacities to separating simple compounds that are difficult to resolve. Recent developments in 2D-LC and 2D-LC–MS have demonstrated the potential of this technique in practice and 2D-LC is set to become an essential tool in the pharmaceutical sector to address problems ranging from coelution, peak purity assessment, simultaneous achiral-chiral analysis, genotoxic impurities, and more.

Supercritical fluid chromatography (SFC) is a well-established analytical technique used in the pharmaceutical industry for decades. However, it is still considered a new technique in some areas, for example, implementing the technique for purity profiling in late-stage development and production. In pharmaceutical analytical departments, SFC serves a wide variety of purposes, including compound purification, purity profile, and chiral analysis. Depending on the phase of drug development, the analytical performance requirements, such as speed of analysis, efficiency, and sensitivity, may vary considerably. The end goal is to provide robust, reliable and transferable analytical SFC methods. The challenges for future development and widespread implementation of SFC and the implementation of SFC in quality control (QC) laboratories using modern instrumentation are also discussed.

These ten propositions are widely acknowledged, but frequently neglected, by practitioners of high performance liquid chromatography (HPLC).

Researchers from Merck and Agilent Technologies have developed a simple and fast generic gas chromatography–flame ionization detection (GC–FID) method for the quantitation of volatile amines in pharmaceutical drugs and synthetic intermediates.

Comprehensive two-dimensional liquid chromatography (2D-LC) was used for detailed profiling of various nonionic ethoxylated surfactants applied in pharmaceutical formulations. Hydrophilic-interaction chromatography (HILIC) and reversed-phase liquid chromatography (LC) were used as the first and second dimensions, respectively. Detection was performed with evaporative light-scattering detection (ELSD) for general profiling and with single-quadrupole mass spectrometry (MS) for structure elucidation of individual peaks and for class-type confirmation of peak-groups.

With the growing use of illegal opioids, analysts should be prepared for a large influx of samples in their laboratories. While the workload may be increasing, the number of analysts and equipment may not, so the need for faster and better liquid chromatography–mass spectrometry (LC–MS) methods is important. By implementing an efficient sample preparation technique for matrix cleanup for some of the most common and traditional opioid matrices-blood and urine-coupled with a rapid and accurate LC method, laboratories can address the analytical needs for this growing problem.

The drug discovery process can be accelerated by chromatographic profiling of analogs by measuring their nonspecific binding to proteins and lipids and then by modelling in vivo distribution. A balanced potency and chromatographically determined membrane and protein binding ensure the selection of compounds with the highest probability to show the desired in vivo distribution behaviour for efficacy and reduced toxicity. The first part of the article will discuss the high performance liquid chromatography (HPLC)-based measurements of lipophilicity and biomimetic properties, while the second part will discuss the models derived from the measured data of known drug molecules and drug discovery compounds.

Chromatographic method development for pharmaceutical analysis can benefit from in silico steered serial coupling of column segments containing different stationary phases of varying length. Contrary to column coupling through trial and error, in stationary-phase optimized selectivity (SOS)-based chromatography the retention of all solutes is predicted for all possible column combinations allowing a rational selection of the optimal column combination. The possibilities of the strategy now surpass the initial usage in isocratic high performance liquid chromatography (HPLC) on dedicated commercial column segments, and allow applications in gradient-, green-, preparative-, and in supercritical fluid chromatography (SFC) on conventional column hardware. Current possibilities, pharmaceutical applications, a downloadable algorithm, and weaknesses of the approach are discussed to allow broader implementation of this methodology in separation science.

Significant recent advances now enable routine usage of HDX-MS for comparing the conformations of biopharmaceutical products.

HIC analysis is carried out using a reversed salt gradient, starting with a high salt concentration and moving to low salt concentration to facilitate protein elution.

Chromatographic techniques with mass spectrometric detection are important enablers in modern drug discovery. With the development of robust instrumentation and implementation of user-friendly software (or software packages), non-expert users can now walk up to easily accessible advanced chromatographic systems and perform experiments at their own convenience. Although remarkable improvements in robustness and ease-of-use have happened since the introduction of the first high performance liquid chromatography–mass spectrometry (HPLC–MS) systems, the instrument performance still needs to be qualified and monitored to ensure consistent high-quality results. This article will demonstrate how a simple test mixture of carefully selected compounds can facilitate both the development of generic ultrahigh-pressure liquid chromatography–mass spectrometry (UHPLC–MS) methods and automated performance monitoring of multiple instruments located in separate laboratories and buildings.

All agencies have issued varying guidances for the approval of recombinant, biosimilars of biopharmaceuticals. However, their impact or meaning is in our understanding and that all submittals are considered on a case-by-case basis.

Quantitative determination of the counterions associated with pharmaceutical salts is a mandatory requirement for quality control. While ion chromatography (IC) is the standard technique in most laboratories, capable of delivering excellent sensitivity, specificity and flexibility, there are other simpler and quicker analytical methodologies that may should be considered for this quality control application.