Consumer marketing approaches are creeping into the marketing of scientific instruments. With a careful approach, you can cut through the hype.
The primary goal of early phase development is to gain a fundamental knowledge of the chemistry of drug substances and drug products to facilitate optimization of synthetic schemes and drug product formulations. At the same time, methods are required for release and stability studies to support clinical trials. Ultimately, the knowledge gained during early development translates into designing control methods for commercial supplies. Our approach to meeting this challenge is based upon the use of a primary method along with orthogonal methods. This paper will discuss the overall strategy, with an emphasis on the chromatographic conditions selected to provide systematic othogonality for a broad range of drugs. Case studies will be presented to demonstrate the utility of orthogonal methods to resolve issues that could not have been addressed using a single release and stability method.
The quantitative performance of the latest generation of high-resolution instruments is comparable to that of a triple quadrupole MS, even though different scanning modes are used. Higher-resolution instrumentation also allows flexibility concerning compound identification because the experiment can be set up for targeted quantitation, screening, or both. In an Orbitrap-based instrument, the parallel reaction monitoring (PRM) mode performs most closely to a triple quadrupole mass analyzer using selected reaction monitoring (SRM) mode. This study looks at the performance of an Orbitrap-based LC–MS method for EPA Method 539.
The guest columnists continue their examination of how statistically rigorous QbD principles can be put into practice.
Multidimensional chromatography, or comprehensive chromatography, is a well-established technique for the analysis of complex mixtures. However, the technique is often perceived as highly complex and difficult to put into practice for routine applications. Nonetheless, the technique provides exceptional potential for addressing challenging separations. The addition of a dilution factor allows multidimensional chromatography to provide a high level of flexibility and selectivity. The dilution effect is achieved by using a column chemistry format compatible with large flow rates, which now offers the option of large volume injection without volume or mass overload issues. This novel solution can reduce or eliminate the need to add a solvent exchange step, such as evaporation or reconstitution, which significantly reduces the most time-consuming part of the sample preparation process.
Mercury pollution mainly originates from industrial activities such as chlorine production, garbage incineration and above all coal-fueled power generation. The US Environmental Protection Agency (US EPA) considers mercury as highly toxic with a pronounced accumulative and persistent character.
In this article, the authors discuss the need for protection against chemical attacks and the role of passive imaging spectroradiometers in the detection of remote chemical agents.
Root diseases caused by soilborne plant pathogens are responsible for billions of dollars of losses annually in food, fiber, ornamental, and biofuel crops. The use of pesticides often is not an option to control plant diseases because of economic factors or potential adverse effects on the environment or human health. For this reason, many Americans are now buying pesticide-free organic foods. Organic agriculture has few options for controlling pests and thus must make full use of natural microbial biological control agents in soils that suppress diseases.
A fast, selective, and reproducible high performance liquid chromatography (HPLC) method was developed and validated for the analyses of third-generation cephalosporin antibiotics, namely, ceftriaxone, cefixime, and cefdinir in human plasma. The analysis was carried out on a 150 mm Ã- 4.6 mm, 5.0-µm C18 column. The mobile phase used was 80:20 (v/v) 50 mmM phosphate buffer (pH 5.0)–methanol at a flow rate of 1.0 mL/min with 230-nm UV detection.
Mycotoxins, toxic secondary metabolites of several fungal species, represent food safety issues of high concern. Deoxynivalenol, the most abundant trichothecene mycotoxin, can be found worldwide as a contaminant of wheat, barley, maize and other cereals (1,2). The transmission of deoxynivalenol from barley into beer has been reported in several studies (3,4). Therefore, its levels should be controlled.
Successful characterization of protein posttranslational modifications (PTMs) is critical to our understanding of many biological processes. Unfortunately, attempts to describe PTMs often prove experimentally difficult and result in ambiguous conclusions. As technologies in the field of mass spectrometry (MS) continue to improve, people are turning increasingly to mass spectral techniques for PTM characterization. Recently, novel modes of peptide fragmentation have emerged that are giving scientists greater ability to elucidate protein posttranslational modification. One example is electron-capture dissociation (ECD), an alternative fragmentation mechanism for use in peptide analysis via tandem mass spectrometry. ECD selectively cleaves N-Cα bonds of the peptide backbone, yielding c- and z-ions without the loss of labile PTMs. ECD therefore holds advantages over conventional fragmentation techniques such as collisionally induced dissociation (CID), which often cleave PTMs from the peptide backbone,..
This review discusses recent technological advances in classical heart-cuttting two-dimensional gas chromatography (GC–GC). These developments are then illustrated by application to analysis of important flavour compounds at trace levels in very complex matrices
High Throughput Sample Preparation Method for Drugs of Abuse in Urine
Rapid sample preparation using the CUSTODIONâ„¢ solid phase microextraction (SPME) syringe was applied to chemical warfare agents (CWAs), CWA simulants, by-products, and precursors. The samples were analyzed quickly and reliably with a sample-to-sample cycle time of less than 3 min using the GUARDIONâ„¢-7 portable capillary gas chromatograph toroidal ion trap mass spectrometer (GC–TMS).
In the past decade, supercritical fluid chromatography (SFC) has experienced a striking resurgence and exponential growth in acceptance, particularly in pharmaceutical and chemical laboratories. In SFC, "supercritical" CO2, in combination with one or more polar organic solvents, most commonly alcohols, are used as mobile phase. The polarity of CO2 is similar to that of hexane, and thereby making SFC a normal phase chromatographic technique. SFC has readily lent itself as an attractive complement to reversed phase HPLC (RPLC). For instance, in separating polar compounds that have little retention, and/or selectivity, even with special polar group embedded columns, SFC holds a unique advantage over RPLC due to its normal phase separation mechanism.
The analysis of polar compounds in support of clinical and preclinical pharmacokinetic studies requires an analytical methodology capable of achieving ultra-low detection and quantification limits. The high sensitivity afforded by coupling HPLC with tandem mass spectrometry (MS–MS) has made it the technique of choice in this environment, but it is subject to the following limitations when reversed-phase liquid chromatography (RPLC) is used
CCC is an excellent alternative to avoid the problems associated with solid-phase adsorbents, which include irreversible adsorption of sample and the need to replace expensive columns. As a result, CCC is gaining popularity as a purification tool.
This article discusses instruments that can be used in the field to rapidly and accurately identify various explosives and their precursors.
Drug discovery scientists are continually striving to improve productivity and efficiency in their workflows. From early discovery to clinical development, existing workflow bottlenecks represent an opportunity to develop solutions to speed the process and improve productivity. The key requirements for quantitative analysis are precision, accuracy, and linear dynamic range. With any quantitative instrument, the hope is that it will be applicable to a vast range of coumpounds, ruggest, and fast. New mass spectrometry (MS) technologies are being developed that meet these criteria and permit high throughput while enabling its application to areas in which speed limitations previously curtailed its practicality. In particular, in the area of ADME profiling, new MS platforms are becoming available that increase the throughput by at least 25-fold, by combining the speed of matrix-assisted laser desorption ionization (MALDI) with the specificity of triple-quadrupole MS. This is bound to greatly accelerate the ADME..
This application note examines the selectivity differences between three L1 columns. The CORTECS Premier C18, CORTECS Premier C18+ and CORTECS Premier T3 Columns were used to separated paracetamol and its impurities using EP monograph conditions.
Guest authors show how mixed modes can be used successfully in the optimization of protein purification, and discuss how various experimental parameters can be used to regulate the binding of proteins to mixed-mode sorbents.
In this article, the authors discuss the need for protection against chemical attacks and the role of passive imaging spectroradiometers in the detection of remote chemical agents.
The current state of economic affairs is tumultous; as the economy struggles to bounce back, companies across all industries are becoming more creative in finding ways to reduce costs without sacrificing the quality of their goods or services. According to a recent survey conducted by the Society of Forensic Toxicologists (SOFT), 64.5% of forensic labs surveyed are implementing changes, or plan to implement changes, as a result of limited resources.
Ramipril impurities D and E are well-known degradation products of ramipril in the finished dosage form. A significant amount of an additional impurity was detected in ramipril tablets by an isocratic reversed-phase high performance liquid chromatography (HPLC) method on a short column. The structure of this impurity was proposed based on liquid chromatography–mass spectrometry (LC–MS) data using an electron spray ionization source. Structural elucidation using nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy was facilitated by a newly developed preparative isolation method. This impurity was characterized as (2R,3aR,6aR)-1-[(R)-2-[[(R)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]propanoyl]octahydrocyclopenta[b]pyrrole-2-carboxylic acid (impurity L). Its identification, synthesis and characterization are discussed.