## Abstract Metabolic activation of drug candidates to electrophilic reactive metabolites that can covalently modify cellular macromolecules may result in acute and/or idiosyncratic immune system‐mediated toxicities in humans. This presents a significant potential liability for the future developme
Mass spectrometry as a technique for testing the purity of drugs for biological use: The case of new antitumor cyclophosphazenes
✍ Scribed by Bernard Monsarrat; Jean-Claude Promé; Jean-François Labarre; François Sournies; Johan C. van de Grampel
- Publisher
- John Wiley and Sons
- Year
- 1980
- Tongue
- English
- Weight
- 413 KB
- Volume
- 7
- Category
- Article
- ISSN
- 1076-5174
No coin nor oath required. For personal study only.
✦ Synopsis
Mass spectrometry has been used for testing the chemical purity of some new antitumor cyclophosphazene compounds. The spectrum qf N3P3Az6 (code name MYKO 63)-which exhibits noticeable activity on murine P 388, L 1210 and B 16 tumors-appeared to be remarkably simple, as most of the fragmentations arose from successive losses of the aziridino radicals. Traces of the pentaziridinomonochloro impurity formed by an incomplete substitution of N3P3CIL chlorine atoms under aziridinolysis could be detected in an impure and toxic sample by spectral subtraction. Quantification of this impurity was performed by selected ion monitoring in the direct inlet mode of sample introduction. The mass spectra of other derivatives of this class of compounds are slightly more complex, since the decomposition pathways showed more intense H-transfers associated with the loss of substituents.
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