Effect of incomplete removal of the tert-butoxycarbonyl protecting group during synthesis of a pharmaceutical drug substance on the residual solvent analysis.
During development of the residual solvent method using headspace-GC for a drug substance, an unexpected peak was observed in the chromatography. GC-MS analysis confirmed the unknown peak identity as isobutylene. An understanding of the source of the isobutylene was required in order to develop appropriate impurity and residual solvent control strategies for the drug substance. The experiments performed to determine the source of the isobutylene peak observed in the headspace-GC chromatography and how the tert-butoxycarbonyl (BOC) de-protection step used in the drug substance synthesis contributes to its observation are discussed.
Beilin
Eugene
E
Eli Lilly Canada Inc, 3650 Danforth Ave, Toronto, Ontario M1N 2E8, Canada.
Baker
Lee J
LJ
Aikins
James
J
Baryla
Nicole E
NE
D000475:Alkenes / Q000032:analysis / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004340:Drug Contamination; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis* / Q000737:chemistry; D012997:Solvents / Q000032:analysis; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry
D000475:Alkenes; D004364:Pharmaceutical Preparations; D012997:Solvents; D014867:Water; C008176:isobutylene