Liquid chromatography-mass spectrometry using the hydrogen/deuterium exchange reaction as a tool for impurity identification in pharmaceutical process development.
HPLC-MS employing deuterium oxide and common MS-compatible deuterated additives in the mobile phase with electrospray ionization is shown to be a viable approach for the structural elucidation of impurities in pharmaceutically active agents following initial studies with protic mobile phases. This approach incorporates the hydrogen/deuterium (H/D) exchange reaction where deuterium is substituted for hydrogen at labile sites. Some developmental compounds studied include an amide, amine, lipopeptide, indole and methyl sulfone. H/D exchange is rapid and the chromatographic performance using deuterated mobile phases is comparable to protic counterparts.
Merck Research Laboratories, Analytical Research Department, P.O. Box 2000, RY 818-B112, Rahway, NJ 07065, USA. thomas_novak@merck.com
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Helmy
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D000077336:Caspofungin; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003903:Deuterium / Q000737:chemistry*; D054714:Echinocandins; D006859:Hydrogen / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry; D055666:Lipopeptides; D010456:Peptides, Cyclic / Q000032:analysis / Q000592:standards; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013450:Sulfones / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods
D054714:Echinocandins; D007211:Indoles; D055666:Lipopeptides; D010456:Peptides, Cyclic; D013450:Sulfones; D006859:Hydrogen; D003903:Deuterium; D000077336:Caspofungin