Special Issues-07-01-2008

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.

Over the last 10 years, several solvent-free microextraction techniques for gas chromatography (GC) and mass spectrometry (MS) have been developed. Two of these techniques, solid-phase microextraction (SPME) and stir-bar sorptive extraction (SBSE), are available commercially for the analysis of volatile compounds, such as flavors in foods and beverages, and toxic organic compounds in environmental applications. Other techniques, such as open tubular trapping, inside needle capillary adsorption trap (1), in-tube SPME, capillary microextraction, needle trap, and headspace solid-phase dynamic extraction (2), were also developed for different applications. The basic principle for all of these techniques is essentially the same. Volatile and semivolatile compounds are adsorbed on a sorbent coating, often packed on the interior surface of a capillary column or stainless steel needle. After the sample is concentrated on the coating, the compounds are desorbed thermally in the heated injection port of a gas..

Automated solid-phase extraction (SPE) has been used extensively with liquid chromatography–tandem mass spectrometry (LC–MS-MS) to facilitate high-throughput analysis in the pharmaceutical, diagnostic, and forensic toxicology areas. In this work, we demonstrate the use of a systemized approach to SPE method development and LC–MS-MS analysis. This approach provides dramatic savings in analysis time and takes advantage of new innovations in high performance liquid chromatography (HPLC) columns to provide the cleanest extracts for LC–MS injection.

Illegal drug use worldwide is at an all-time high. There is a crucial need for fast and accurate analysis to positively identify suspected drugs in criminal investigations. Gas chromatography combined with time-of-flight mass spectrometry (GC–TOFMS) can be a valuable tool for drug testing in forensic crime laboratories. Method development and GC–TOFMS experimentation was conducted in cooperation with a local crime laboratory. The laboratory testing presented will illustrate highly efficient methods and data developed for crime labs that assist in the battle against illegal drugs. Many drug classes have chemical properties that present particular analytical challenges, such as poor detector response, chemical lability, or poor chromatographic peak shape. This article presents GC–TOFMS methods developed for several major drug classes and chemical functionalities. The major drugs included in the initial method development are methamphetamine, ecstasy, and heroin. Robust and accurate..

Special Issues

July 01, 2008

A summary of the five-day mass spectrometry conference held this month in Denver, Colorado.

This article describes the ability to increase the sensitivity for a target compound in the presence of high-level background impurities by removing the dosing vehicle using a high-field asymmetric waveform ion mobility spectrometry gas-phase separation before mass spectrometry analysis.

Liquid chromatography with tandem mass spectrometry (LC–MS-MS) led to a revolution in environmental testing. The coupling of liquid chromatography with tandem mass spectrometry created a powerful analytical tool for the analysis of emerging environmental contaminants. Pharmaceuticals and personal care products, perfluorinated compounds, brominated flame retardants, and disinfection byproducts were chosen as examples to illustrate the use of this new technique in environmental analysis.

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,..