The use of shift reagents in ion mobility-mass spectrometry: studies on the complexation of an active pharmaceutical ingredient with polyethylene glycol excipients.
Gas-phase ion mobility studies of mixtures containing polyethylene glycols (PEG) and an active pharmaceutical ingredient (API), lamivudine, have been carried out using electrospray ionization-ion mobility spectrometry-quadrupole-time-of-flight mass spectrometry (ESI-IMS-Q-TOF). In addition to protonated and cationized PEG oligomers, a series of high molecular weight ions were observed and identified as noncovalent complexes formed between lamivudine and PEG oligomers. The noncovalent complex ions were dissociated using collision induced dissociation (CID) after separation in the ion mobility drift tube to recover the protonated lamivudine free from interfering matrix ions and with a drift time associated with the precursor complex. The potential of PEG excipients to act as "shift reagents," which enhance selectivity by moving the mass/mobility locus to an area of the spectrum away from interferences, is demonstrated for the analysis of lamivudine in a Combivir formulation containing PEG and lamivudine.
Howdle
Mark D
MD
Centre for Analytical Science, Department of Chemistry, Loughborough University, Leicestershire, United Kingdom.
Eckers
Christine
C
Laures
Alice M-F
AM
Creaser
Colin S
CS
D000465:Algorithms; D019380:Anti-HIV Agents / Q000737:chemistry*; D002412:Cations / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004338:Drug Combinations; D005079:Excipients / Q000737:chemistry*; D019259:Lamivudine / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011522:Protons; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry; D015215:Zidovudine / Q000737:chemistry
D019380:Anti-HIV Agents; D002412:Cations; D004338:Drug Combinations; D005079:Excipients; D011522:Protons; C109078:lamivudine, zidovudine drug combination; D019259:Lamivudine; D011092:Polyethylene Glycols; D015215:Zidovudine