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then withdrew it. “That’s what I thought,” Goldman said.
MALDI for QC In another conference workshop, researchers revealed that considerable progress has been made toward the use of MALDI MS for identity testing in a quality control (QC) setting. “People want to eliminate running a conventional peptide map, and this is an alternative they are exploring,” said workshop co-chair Rohin Mhatre of Biogen, in a later interview. In theory, it has always been possible to use MALDI for QC, but questions of reproducibility have made it an unlikely candidate in reality. The biggest issue has been whether it’s possible to validate MALDI methods, Mhatre explained. “Two years ago, I don’t know that many people would have said yes,” he added. “But when we asked how many people [in this workshop] are using MALDI or were considering it for release assays, I was surprised to see that several were.” Although nobody has put MALDI into a QC lab and used it to release a product, several researchers have been using it in a development lab with the idea of eventually moving it into release, said Mhatre. MALDI’s ultimate fate will depend on whether researchers can get all the information they need from it and how comfortable they are doing the tests, he said. “But there is hope, and significant steps have been taken in that direction,” he added.
Accelerator MS for biologics To begin a talk with a list of problems with 14C almost isn’t fair, but Colin Garner of the United Kingdom’s Centre for Biomedical Accelerator MS did it anyway. There is the long half-life, the need for large doses, and the special facilities required for making radiolabels. When radioactivity is used in clinical settings, there are the added issues of
obtaining permission; administering radioactivity to troublesome areas, such as the lungs; and the problem of discharging “hot” patients or subjects. An alternative that is receiving increasing attention in biological studies is accelerator MS (AMS). Originally developed for radiocarbon dating, AMS uses a 10,000-V tandem van der Graff accelerator to analyze negative ions. An AMS can count to the zeptomole level—which means that the efficiency of sample preparation doesn’t matter much—and uses little or no radioactivity, Garner said. (Radioactive or not, isotopes that are stable for at least 10 years and are rare in the environment will work.) The use of low levels of radioactivity has many advantages. First, AMS makes it possible to study the impact of putative toxins or carcinogens at realistic levels of exposure, rather than giving
large doses and extrapolating back to the low ones. Second, because a variety of tags can be used, it is easier to look at the interactions of multiple compounds. And third, in clinical studies of new drugs, AMS can cut the dose of radioactivity administered to 1/1000th of the usual dose or, as Garner described it, the “homeopathic” level. In fact, Garner added, administering such low levels of radioactivity— which are equivalent to ~10 min of natural cosmic exposure—does not require external regulatory approval in the United Kingdom. Permission from an institutional review board is enough. This situation raises several possibilities of interest to drug companies, including giving small doses of drugs to humans earlier than usual and allowing studies in previously forbidden populations, such as children and women of child-bearing age.
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