Mass spectrometry - Articles and news items

Mass Spectrometry: In-depth focus 2013

Latest issue, Supplements / 17 April 2013 / Uwe Christians, Jelena Klawitter, Jost Klawitter, George McLeod, Min Yang

This free to view Mass Spectrometry in-depth focus is supported by AB Sciex, Bruker and Shimadzu:

• Corticosteroids and mass spectrometry; latest applications using LC/MS³
  (András Szeitz Faculty of Pharmaceutical Sciences, University of British Columbia)
  The adrenals were identified in man more than 400 years ago, but in the following few hundred years, not much progress was made to learn about their role1. This delay was certainly made up for by the remarkably quick development of the corticosteroids (CSs), the hormones of the adrenals, beginning with their isolation from the adrenal glands in the late 1920s to their widespread use as therapeutic agents in the present day. CSs can be analysed by several methodologies, and this brief review is focused on the mass spectrometry techniques for the determination of CSs in a variety of matrices.
• Multi-analyte LC-MS/MS assays for the quantification of endogenous compounds during the development of drugs and companion diagnostics – the beauty and the beast
  (Uwe Christians, Jelena Klawitter and Jost Klawitter, iC42 Integrated Solutions for Systems Biology in Clinical Research and Development, Department of Anesthesiology, University of Colorado Denver)
  Personalised medicine is an intriguing concept and constitutes a paradigm shift in medicine. Abandoning the blockbuster drug concept will not only require the development of safer and more efficacious drugs that are focused on the individual patient’s genotype and/or phenotype, it also requires the development of new context-specific diagnostic tools that provide biological or clinical information that allows for better decision-making about the development and use of a drug, so-called context dependent biomarkers and companion diagnostics. Once approved together with a drug, companion diagnostics are used to predict if an individual patient will benefit from this drug or not.
• Q&A
  George McLeod, Market Manager, Pharmaceutical and Structural Chemistry, Bruker Daltonic sits down with Min Yang, UCL School of Pharmacy to answer his questions on mass spectrometry.
• Show preview – European Lab Automation (ELA) 2013 Conference and Tradeshow
  Select Bio is delighted to announce that the European Lab Automation (ELA) 2013 Conference and Tradeshow will open its doors from 6 June 2013. A two day, five track congress, the event offers over 75 scientific presentations on automation and its application within life science, alongside more than 100 equipment vendors and supporting companies, and an over 1,000 expected visitors. ELA provides life science researchers and professionals with an unparalleled opportunity to encourage technological discussions and scientific collaboration.
• Show preview – ASMS Conference on Mass Spectrometry and Allied Topics
  The 61st ASMS Conference on Mass Spectrometry and Allied Topics will take place from 9 – 13 June at the Minneapolis Convention Center, Minnesota, USA. The American Society for Mass Spectrometry sponsors the conference, which will be attended by more than 6,500 scientists. Approximately 3,000 papers will be presented as posters and talks. (more…)

Future trends in drug discovery technology

Issue 6 2012 / 18 December 2012 / Terry McCann, TJM Consultancy

The average cost to a major pharmaceutical company of developing a new drug is over USD 6 billion1. Herper1 observes that the pharmaceutical industry is gripped by rising failure rates and costs, and suggests that the cost of new drugs will be reduced by new technologies and deeper understanding of biology. While the objectives of drug discovery don’t change, the methods and techniques by which pharmaceutical companies, biotechs and academia discover new drugs are evolving at a significant pace – and they need to.

Drug discovery scientists are all aiming to identify compounds and candidate drugs with ‘good’ properties that are safe and efficacious, as quickly and cheaply as possible. The standard approach of the last 20 years has been to identify a single molecule disease target, and then to identify a compound that interacts with and modulates this target with high specificity. However, there is now a growing realisation that this ‘one target – one drug’ approach doesn’t work well, and that screening huge libraries of compounds against one particular property of an isolated target is an inefficient way to discover potential drugs. Much of the innovation currently seen in drug discovery methodologies seeks to access and integrate more information – about targets, compounds, and disease phenotypes – to enable a more comprehensive and holistic approach to discovering ‘good’ drug candidates. This article does not try to crystal ball-gaze deep into the future, but rather to identify those trends in the adoption of new technologies and approaches that are gaining traction now, and that can be expected to become more prevalent in the next two to three years. (more…)

MS-based methods for detection, quantitation and localisation of pharmaceuticals and metabolites in biological samples

Issue 6 2012 / 18 December 2012 / Tyler Greer, Department of Chemistry, University of Wisconsin-Madison and Lingjun Li, Department of Chemistry & School of Pharmacy, University of Wisconsin-Madison

Mass spectrometry is a powerful, multi-faceted technique capable of analysing pharmaceuticals and their metabolites in biological matrices. Although it is more commonly applied to proteins, peptides and lipids, an increasing number of studies use mass spectrometry based techniques to detect, quantitate and localise pharmaceuticals and their metabolites. The availability of functionally unique ionisation methods and preparative separation options coupled with the specificity and sensitivity of a mass analyser make mass spectrometry an attractive option in pharmaceutical studies involving biofluids and tissue. This review aims to provide a general description of the primary mass spectrometric and preparative steps used to analyse pharmaceuticals in biological systems.

A leading concern in drug discovery is the potential reactivity of metabolites, which can be biologically transformed from stable pharma – ceutical products. Drug metabolites are often considered to be potentially toxic because of their ability to covalently modify proteins and DNA. For this reason, pharmaceutical developers create methods to assess the propensity of new drugs to degrade into reactive metabolites and gauge the effects these metabolites have1. Another area of study, pharmaceutical meta – bolomics, typically compares the endogenous metabolites of control specimens with drugadministered specimens2. Mass spectrometry has emerged as a useful tool in these two areas because of its throughput, sensitivity and ability to identify multiple molecules in biological media. (more…)

In-depth focus – Mass Spectrometry

Issue 2 2012, Supplements / 25 April 2012 / Ana Rita Angelino, Min Yang, Tasso Miliotis, Constanze Hilgendorf, Anthony Bristow, George McLeod, Detlev Hochmuth, Alessandro Baldi, Gary Harland

This free to view Mass Spectrometry in-depth focus is sponsored by Waters, Bruker, Protea and Dr. Hochmuth and contains the following articles:

• Mass spectrometry in drug discovery – Proteomics, small molecules and metablomics
  (Ana Rita Angelino and Min Yang, Department of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy)
• Quantification of membrane drug transporters and application in drug discovery and development
  (Tasso Miliotis and Constanze Hilgendorf, Innovative Medicines, AstraZeneca R&D)
• Show preview – The 60th annual conference on Mass Spectrometry and Allied Topics
• Anthony Bristow, AstraZeneca, poses the questions for our Mass Spectrometry Leaders Roundtable
  (George McLeod, Market Manager, Pharmaceutical MS, Bruker Daltonics / Detlev Hochmuth, Scientific Consultant and Software Developer for MS and Chemoinformatics, Dr. Hochmuth Scientific Consulting / Alessandro Baldi, VP & General Manager, Protea Biosciences Inc / Gary Harland, Mass Spectrometry Product Manager, Waters Corporation)

(more…)

Recent developments in the use of LCMS in process pharmaceutical chemistry

Issue 1 2012 / 28 February 2012 / Dr. Florence O. McCarthy, Department of Chemistry, Analytical and Biological Chemistry Research Facility, University College Cork

Liquid Chromatography Mass Spectrometry (LCMS) is a powerful technique that has recently undergone exponential growth in its application to pharmaceutical synthesis. This perspective will outline the general principles of LCMS, detail some recent approaches and the benefits to be derived from its use at an early stage of process development.

Identification of the components in a mixture is the primary function of analytical chemistry and there are a range of techniques available. When the solution to this problem requires some structural identity, LCMS is the instrument of choice.

Liquid Chromatography Mass Spectrometry is defined as the use of the separating properties of liquid chromatography combined with a detector capable of mass analysis (mass spectrometer: single quadrupole, triple quadrupole, ion trap, Time Of Flight, Q-TOF etc.). This combination may be configured in many ways, for a general scheme. (more…)

Maldi-mass spectrometry imaging applied to drug discovery and development

Issue 5 2011 / 19 October 2011 / Brendan Prideaux, Dieter Staab, Gregory Morandi, Nicole Ehrhard and Markus Stoeckli, Novartis Institutes for BioMedical Research

Since its introduction in the field of biomedical imaging over 10 years ago1, matrixassisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) has played an ever increasing role in drug discovery and development and is now utilised in laboratories of many leading pharmaceutical companies and collaborating academic institutions.

The need for mass spectrometry imaging in drug discovery is founded on the shortcomings of current technologies. Traditional methods of spatially mapping the distribution of compounds in tissue involved a combination approach of autoradiography (WBA) with metabolite information obtained from LC/MS analysis of tissue homogenate2. Autoradio – graphy methods only monitor the radiolabel and therefore are not able to distinguish the parent drug from its metabolites. The addition of LC/MS allows for conclusive determination of metabolites. However, this only produces spatial information at the whole organ level and not the spatial detail that can be routinely achieved using MSI. (more…)

Detection of microorganisms using optical spectroscopic-based rapid method technologies

Issue 4 2011 / 31 August 2011 / Michael J. Miller, President, Microbiology Consultants, LLC

This is the fourth in a series of articles on rapid microbiological methods that will appear in European Pharmaceutical Review during 2011. Previously, we discussed a number of cellular-component rapid microbiological methods (RMMs), such as ATP bioluminescence, fatty acid analysis, MALDI and SELDI time of flight mass spectrometry, Fourier transform-infrared (FT-IR) spectrometry and technologies that rapidly detect the presence of endotoxins. In the current article, we will review a relatively new set of rapid methods that are based on optical spectroscopy. These technologies are quite exciting, as they do not rely on microbial growth for a response and the time to result can be instantaneous.

Optical spectroscopy is an analytical tool that measures the interactions between light and the material being studied. Light scattering is a phenomenon in which the propagation of light is disturbed by its interaction with particles. There are a number of light scattering principles that may be utilised in rapid method technologies; therefore, it is appropriate to quickly review some of these principles in order to understand the scientific basis for the RMMs that will be discussed later in this article. (more…)

Evolution and revolution in time-of-flight mass spectrometry and its impact on research within the pharmaceutical industry

Issue 3 2011 / 20 June 2011 / Tony Bristow, Pharmaceutical Development, AstraZeneca

Time of flight mass spectrometry (TOF-MS) has been an attractive choice of instrument for many years due to its potentially unlimited m/z range, high-speed acquisition, accurate mass measurement capability and sensitivity. Originally commercialised in the late 1950’s by the Bendix Corporation1, several physical and technical issues of the early TOF instruments limited both mass resolving power and mass accuracy2. From the early 1970’s to the early 1990’s, these limitations were overcome. Initially the advent of reflectron TOF-MS overcame the ion energy spread, hence increasing mass resolution3. The later combination with orthogonal acceleration (oa) can be seen as the catalyst for the vast range of TOF instrumentation that is available today, with greatly improved mass resolving power and mass accuracy4,5. (more…)

MS-based clinical proteomics: biomarker discovery in men’s cancer

Issue 5 2010 / 29 October 2010 / Brian Flatley Dept of Chemistry, University of Reading, Reading and Harold Hopkins Dept of Urology, Royal Berkshire NHS Foundation Trust Hospital, Reading and Peter Malone Harold Hopkins Dept of Urology, Royal Berkshire NHS Foundation Trust Hospital, Reading and Rainer Cramer Dept of Chemistry, University of Reading, Reading

Each year, approximately 10,000 men in the UK die as a result of prostate cancer (PCa) making it the third most common cancer behind lung and breast cancer. Worldwide, more than 670,000 men are diagnosed every year with the disease1. Current methods of diagnosis of PCa mainly rely on the detection of elevated prostate-specific antigen (PSA) levels in serum and/or physical examination by a doctor for the detection of an abnormal prostate. PSA is a glycoprotein produced almost exclusively by the epithelial cells of the prostate gland2. Its role is not fully understood, although it is known that it forms part of the ejaculate and its function is to solubilise the sperm to give them the mobility to swim. Raised PSA levels in serum are thought to be due to both an increased production of PSA from the proliferated prostate cells, and a diminished architecture of affected cells, allowing an easier distribution of PSA into the wider circulatory system. (more…)

Mass spectrometry based proteomics: trends in tools and strategies

Industry Focus 2008, Past issues / 7 April 2008 /

Recent years have seen great upward leaps in the development of mass spectrometry applied to the field of proteomics. Today it is possible to take a complex biological sample such as organelles, cells, tissue or a biofluid, perturbed or stimulated in some way, and identify and quantitate up to several thousand proteins and determine the level of relative change caused by the perturbation or stimulus. The current challenge is not to identify or quantitate proteins in a limited set of samples, but to profile large series (clinical samples, time-course, sub-cellular compartments) at sufficient depth, and to interpret and make biological sense of the data.

At the end of the 1980s, we saw the birth of two new ionization techniques that changed the face of mass spectrometry; electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI). In the 2000s we have seen terrific developments in mass spectrometer design, such as the development of hybrid fourier-transform, the MALDI-TOF/TOF and hybrid triple quadrupole-iontrap (QTrap) mass spectrometers, and recently an entirely new mass analyser, the orbital electrostatic trap that became incorporated in a hybrid platform with an ion trap (Orbitrap)1 (Figure 1). This new instrument allows for great sensitivity, mass accuracy and high-throughput MS/MS. Combined with the new fragmentation technique ‘Electron Transfer Dissociation’, that preserves labile PTMs great advances are expected in the field of signaling research. (more…)

Test method validation for cleaning validation samples

Issue 2 2008, Past issues / 19 March 2008 /

Testing cleaning validation samples requires a validated method. The extent of validation is dependent upon the type of method employed, the capabilities of the method, the scientific and regulatory needs of the resulting data and the anticipated outcome of the testing. A number of test method options are reviewed for their analytical capabilities, along with their method validation parameters.

Cleaning validation is a critical function in pharmaceutical manufacturing. Regulatory agencies have placed great emphasis on demonstrating that a cleaning process prevents cross-contamination1,2. Manufacturing equipment cleanliness does not merely impact the subsequent formulation, but every formulation processed in the equipment and the overall manufacturing program in a facility. A cleaning process is validated and monitored through testing of the equipment. Testing ranges from visual inspection to swab sampling or rinse sampling.

For any test method to be suitable for its intended purpose, it must be appropriate for measuring analytes at and below the acceptable residue limit (ARL). An ARL can be based on available toxicological data such as an allowable daily intake (ADI), an adulteration limit such as 10 ppm and visual cleanliness. The ARL has a direct bearing on the validation parameters of the test method. (more…)