Development, validation and transfer into a factory environment of a liquid chromatography tandem mass spectrometry assay for the highly neurotoxic impurity FMTP (4-(4-fluorophenyl)-1-methyl-1,2,3,6-tetrahydropyridine) in paroxetine active pharmaceutical ingredient (API).
This work describes the development of a liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for a highly toxic impurity, FMTP (4-(4-fluorophenyl)-1-methyl-1,2,3,6-tetrahydropyridine), in paroxetine active pharmaceutical ingredient (API), followed by the subsequent validation of the methodology and transfer into a global production/quality control environment. The method was developed to achieve a detection limit of 10ppb mass fraction of FMTP in paroxetine API. An LC-MS/MS method was chosen because it provided the required sensitivity and selectivity with minimal sample preparation. This paper discusses the issues with transferring such complex methodology to a production environment. Linearity, repeatability and reproducibility of the method were demonstrated. This work shows that it is possible using the same approach that would be used for the transfer of any analytical method from R&D to a manufacturing environment.
GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK.
Phil J
PJ
Borman
Marion J
MJ
Chatfield
Elizabeth L
EL
Crowley
Christine
C
Eckers
David P
DP
Elder
Scott W
SW
Francey
Alice M-F
AM
Laures
Jean-Claude
JC
Wolff
D018687:Antidepressive Agents, Second-Generation / Q000032:analysis / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods*; D004340:Drug Contamination; D004345:Drug Industry / Q000379:methods*; D015394:Molecular Structure; D020258:Neurotoxicity Syndromes / Q000209:etiology; D017374:Paroxetine / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000032:analysis*; D011725:Pyridines / Q000737:chemistry*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
C539352:(4-(4-fluorophenyl)-1-methyl-1,2,3,6-tetrahydropyridine); D018687:Antidepressive Agents, Second-Generation; D004364:Pharmaceutical Preparations; D011725:Pyridines; D017374:Paroxetine