Identification and characterization of potential impurities of quetiapine fumarate.
Seven potential impurities, including by-products, starting materials and intermediates were identified in pharmaceutical substance quetiapine fumarate and characterized by spectroscopic methods (MS, IR, NMR). Based on these methods the structures of the impurities were assigned or confirmed as: impurity I: 2-(phenylthio)aniline; impurity II: phenyl N-[2-(phenylthio)phenyl]carbamate; impurity III: N,N'-bis[2-(phenylthio) phenyl]urea; impurity IV: N-[2-(phenylthio)phenyl]-1-piperazinecarboxamide hydrochloride; impurity V: N,N'-bis[(2-phenylthio)phenyl]-1,4-piperazinedicarboxamide; impurity VI: 11-(1-piperazinyl) dibenzo[b,f][1,4]thiazepine fumarate; impurity VII: 1,4-bis(dibenzo[b,f][1,4] thiazepin-11-yl)piperazine. Structural elucidation of compounds, proposed MS fragmentation pathway and possible ways of formation of the impurities are also discussed.
Stolarczyk
Elzbieta U
EU
Pharmaceutical Research Institute, Warsaw, Poland. e.stolarczyk@ifarm.waw.pl
Kaczmarek
Lukasz
L
Eksanow
Kamil
K
Kubiszewski
Marek
M
Glice
Magdalena
M
Kutner
Andrzej
A
D000814:Aniline Compounds / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D014150:Antipsychotic Agents / Q000032:analysis* / Q000138:chemical synthesis; D002219:Carbamates / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D003987:Dibenzothiazepines / Q000032:analysis* / Q000138:chemical synthesis; D004340:Drug Contamination; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010671:Phenylurea Compounds / Q000737:chemistry; D010879:Piperazines / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D000069348:Quetiapine Fumarate; D013055:Spectrophotometry, Infrared; D013440:Sulfides / Q000737:chemistry; D013841:Thiazepines / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D014508:Urea / Q000032:analysis / Q000138:chemical synthesis
C540414:1,4-bis(dibenzo(b,f)(1,4)thiazpein-11-yl)piperazine; C540413:11-(1-piperazinyl)dibenzo(b,f)(1,4)thiazepine; C540408:2-(phenylthio)aniline; D000814:Aniline Compounds; D014150:Antipsychotic Agents; D002219:Carbamates; D003987:Dibenzothiazepines; C540412:N,N'-bis((2-phenylthio)phenyl)-1,4-piperazinedicarboxamide; C540410:N,N'-bis(2-(phenylthio)phenyl)urea; C540411:N-(2-(phenylthio)phenyl)-1-piperazinecarboxamide; D010671:Phenylurea Compounds; D010879:Piperazines; D013440:Sulfides; D013841:Thiazepines; C540409:phenyl N-(2-(phenylthio)phenyl)carbamate; D000069348:Quetiapine Fumarate; D014508:Urea; C023650:aniline