Quantitation of acetol in common pharmaceutical excipients using LC-MS.
A method for the quantification of acetol at mug/L levels in propylene glycol and glycerol, two common pharmaceutical excipients, was developed and validated. This simple yet highly specific method makes use of derivatization by O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) in aqueous solution at room temperature followed by analysis via LC-MS without sample pre-concentration, extraction, or cleanup. Kinetic studies indicated that the derivatization reaction was complete after 4.5h. Preliminary investigations demonstrate the applicability of this method to the separation and identification of other electrophilic impurities. This suggests the potential for a simple, quantitative assay at room temperature in aqueous solution for the determination of a variety of electrophilic impurities in pharmaceutical excipients, without the need for sample concentration or extraction.
Eli Lilly Canada Inc., Toronto, Ontario, Canada M1N 2E8. BEILIN_EUGENE@Lilly.com
Eugene
E
Beilin
Lee J
LJ
Baker
Paul
P
Culbert
Nicholas P
NP
Toltl
D000096:Acetone / Q000031:analogs & derivatives* / Q000032:analysis; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D005079:Excipients; D004364:Pharmaceutical Preparations; D000096:Acetone; C004433:acetol