LC determination of impurities in methoxsalen drug substance: isolation and identification of isopimpinellin as a major impurity by atmospheric pressure chemical ionization LC/MS and NMR.
A gradient elution LC method was developed to separate methoxsalen from three of its known impurities: isopimpinellin, bergapten, and ammidin. The method employs a methanol-6%THF (aq) mobile phase, phenyl column, and detection at 254 nm. The gradient LC procedure was applied to seven lots of methoxsalen from five different manufacturers. Six of the seven lots tested contained isopimpinellin as the major impurity at a concentration range of 0.2-2.5%. Identification of the impurity as isopimpinellin was accomplished by a combination of analytical and preparative LC, atmospheric pressure chemical ionization liquid chromatography/mass spectrometry, and NMR.
Lehr
Gary J
GJ
Department of Health and Human Services, Food and Drug Administration, Northeast Regional Laboratory, 158-15 Liberty Avenue, Jamaica, NY 11433, USA. glenl@ora.fda.gov
Barry
Thomas L
TL
Franolic
John D
JD
Petzinger
Glenn
G
Scheiner
Peter
P
D004340:Drug Contamination; D011564:Furocoumarins / Q000032:analysis* / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008730:Methoxsalen / Q000032:analysis* / Q000737:chemistry
D011564:Furocoumarins; C015304:isopimpinellin; D008730:Methoxsalen