A generic approach for the determination of residues of alkylating agents in active pharmaceutical ingredients by in situ derivatization-headspace-gas chromatography-mass spectrometry.
A simple, reliable and fast procedure for the simultaneous determination of residues of some common alkylating agents (AAs), such as mesylates, besylates, tosylates and sulfates, employed in drug synthesis, has been developed by in situ derivatization-headspace-gas chromatography-mass spectrometry. Pentafluorothiophenol is used as a derivatizing agent in different water/dimethyl sulfoxide ratios. Compared to former analytical procedures, this approach returns improvements in analysis time, selectivity, analyte stability and method sensitivity (LOD=0.11 microgg(-1) for methyl tosylate). The method exhibits low matrix dependence, excellent accuracy, precision (R.S.D.=2.8-10% range at 1 microgg(-1)) and robustness through the use of deuterated internal standards. Knowledge of the synthetic route allows a targeted approach to the determination of specific AAs since the procedure does not distinguish between acid species. The procedure was successfully applied to different pharmaceutical matrixes, and is particularly suitable for routine analysis with high sample throughput.
Alzaga
Roberto
R
Pfizer Analytical Research Centre, Ghent University, Krijgslaan 281 S4-bis, B-9000 Ghent, Belgium.
Ryan
Robert W
RW
Taylor-Worth
Karen
K
Lipczynski
Andrew M
AM
Szucs
Roman
R
Sandra
Pat
P
D000477:Alkylating Agents / Q000032:analysis*; D004340:Drug Contamination / Q000517:prevention & control; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012015:Reference Standards; D012680:Sensitivity and Specificity; D012997:Solvents / Q000737:chemistry
D000477:Alkylating Agents; D004364:Pharmaceutical Preparations; D012997:Solvents