Analysis of process impurities in the basic drug SB-253149 using capillary electrophoresis and on-line mass spectrometric detection.
Capillary electrophoresis with on-line electrospray ionisation mass spectrometry (CE/ESI-MS) has been used to identify process impurities in a batch of the anti-atherosclerotic drug, SB-253149. The impurities were separated from the main drug compound by capillary electrophoresis (CE) using an ammonium formate buffer at low pH in an untreated fused silica capillary. The CE method was initially developed using UV as the detection mode and then later structural elucidation work was achieved using an ion trap mass spectrometer. To maintain peak resolution and peak shape when the CE system was coupled to the mass spectrometer, a modified capillary cassette linked to a coaxial sheath flow electrospray ionisation (ESI) interface was used. By performing MS/MS experiments in conjunction with chemical knowledge of the reactivities of SB-253149, it was possible to propose molecular structures for impurities detected in the batch of SB-253149. The results from this study revealed that most of the process impurities in SB-253149 were dimeric derivatives of the parent molecule as well as trace levels of the starting material. This type of information was vital in process control and optimisation for the synthetic route for this drug.
Okafo
G
G
SmithKline Beecham Pharmaceuticals, New Frontiers Science Park (North), Harlow, Essex CM19 5AW, UK.
Tolson
D
D
Monte
S
S
Marchbank
J
J
D000924:Anticholesteremic Agents / Q000032:analysis* / Q000138:chemical synthesis; D004340:Drug Contamination; D019075:Electrophoresis, Capillary / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D063065:Organophosphonates; D011725:Pyridines / Q000032:analysis* / Q000138:chemical synthesis
D000924:Anticholesteremic Agents; D063065:Organophosphonates; D011725:Pyridines; C422604:diisopropyl(2,6-dimethyl-3-pyridyl)amine-amino-4(4-hydroxy-3-methoxy-5-methylphenyl)methyl phosphonate