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Archive - Sep 10, 2014

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LC-MS Analysis Shows That Timing of Food Intake Could Impact Effectiveness of TB Treatment

The timing of food intake in the early phase of TB treatment could have a negative impact on the effectiveness of TB treatment. A new study, presented at the European Respiratory Society (ERS) International Congress in Munich on September 7, 2014, suggests that eating food just before taking a TB drug could reduce the effectiveness of the medicine. Researchers conducted a small study looking at 20 patients who were about to begin treatment for TB for the first time. The patients were given the usual course of TB drugs, including isoniazid, rifampicin, pyrazinamide, and ethambutol. The drugs were administered by injection on day one and given orally on days two and three, either while fasting or with a high-carbohydrate meal. Blood samples were taken from each participant and an analytical chemistry technique, called liquid chromatography-tandem mass spectrometry, was used to separate the sample and give information about the chemicals present. This technique allows the researchers to assess concentration levels of the drug and fraction of the unchanged drug that reaches the circulation. Blood samples were taken from the same individual and in the same environment while changing the food intake. The results showed that when the drugs were given with a high-carbohydrate meal, there were lower concentrations of isoniazid, rifampicin, and pyrazinamide in the blood compared with when they were given the drugs in a fasting state. This suggests that eating a high-carbohydrate meal, before taking the drugs can make the drugs less effective. Antonia Morita Iswari, lead author from the Universitas Gadjah Mada in Indonesia and currently completing her Ph.D.

Fungal Leucinostatins Identified Using LC-MS/MS

The fungus Paecilomyces lilacinus (image) produces leucinostatins, which are peptaibiotics that exert a range of biological activities, including antimalarial, antiviral, antitumor, and phytotoxic activities. In an article published online on September 3, 2014 in The Journal of Antibiotics, Dr. Ana Martinez and Dr. Luiz Moraes, of the University of Sao Paulo in Brazil, report the development of an analytic method utilizing LC-MS/MS in the precurson ion and product ion modes to identify five new leucinostatins from this fungus. The scientists used Direct Infusion-MS (DI-MS) to help identify the most abundant leucinostatins (F, D, B2, S, A, and K). They noted that MS/MS analysis using a triple quadrupole operating at different scan modes is a versatile tool with which to study natural products, especially peptaibiotics. They commented that although DI-MS full-scan analysis is both rapid and sensitive, it cannot distinguish between peptide isomers. On the other hand, although LC-MS/MS operated in the precursor ion and product ion modes is time-consuming, it does allow the identification of the structures of isomers or isobars in a crude extract. [The Journal of Antibiotics abstract]

AB Sciex and Dalton Collaborate to Develop Antibody-Drug Conjugate Analysis Capabilities

In an August 26, 2014 press release, AB Sciex announced that it has established a research collaboration with Dalton Pharma Services (Dalton) to develop Antibody-Drug Conjugate (ADC) analysis capabilities. This will include development of a more definitive and comprehensive method for the identification of drug loading and position of conjugation on macromolecules. This collaboration is part of AB SCIEX's commitment to support the growing movement to bring targeted antibody-based therapies to market. The collective goal is to help our customers bring drugs from concept to market faster. The collaboration provides AB SCIEX, a global leader in life science analytical technologies, with the specialized synthetic conjugation capabilities of Dalton. The research includes the preparation and characterization of ADC’s by Dalton scientists working with AB SCIEX experts to develop standardized analytical procedures on the TripleTOF® 5600+ system with SelexION™ technology and the new TripleTOF® 6600 platform (image) for determining the chemical structures of conjugated molecules. "A key challenge for developing successful Antibody-Drug Conjugate medicines is understanding the structure and payload of the final molecule. Determining where the drug attaches to a particular antibody early in its development and the number of drug molecules on the antibody are important indicators of the likely success of a new ADC," explained Dr. Tan Quach, Chemistry Manager at Dalton Pharma Services. "Recent advances in mass spectrometry (MS) have provided a solution to answer the challenging questions in terms of understanding ADC drug development and working within a biological matrix,” said Dr. Chris Radloff, Vice President, LC/ MS Business at AB SCIEX.