A practical derivatization LC/MS approach for determination of trace level alkyl sulfonates and dialkyl sulfates genotoxic impurities in drug substances.
Derivatization LC/MS methodology has been developed for the determination of a group of commonly encountered alkyl esters of sulfonates or sulfates in drug substances at low ppm levels. This general method uses trimethylamine as the derivatizing reagent for ethyl/propyl/isopropyl esters and triethylamine for methyl esters. The resulting quaternary ammonium derivatization products are highly polar (ionic) and can be retained by a hydrophilic interaction liquid chromatography (HILIC) column and readily separated from the main interfering active pharmaceutical ingredient (API) peak that is usually present at very high concentration. The method gives excellent sensitivity for all the alkyl esters at typical target analyte level of 1-2 ppm when the API samples were prepared at 5mg/mL. The recoveries at 1-2 ppm were generally above 85% for all the alkyl esters in the various APIs tested. The injection precisions of the lowest concentration standards were excellent with R.S.D.=0.4-4%. A linear range for concentrations from 0.2 to 20 ppm has been established with R(2)>or=0.99. This general method has been tested in a number of API matrices and used successfully for determination of alkyl sulfonates or dialkyl sulfates in support of API batch releases at GlaxoSmithKline.
An
Jianguo
J
Department of Analytical Sciences, GlaxoSmithKline Pharmaceutical Research and Development, UW2940, P.O. Box 1539, 709 Swedeland Road, King of Prussia, PA 19406, USA.
Sun
Mingjiang
M
Bai
Lin
L
Chen
Ted
T
Liu
David Q
DQ
Kord
Alireza
A
D000476:Alkanesulfonates / Q000032:analysis*; D002853:Chromatography, Liquid / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004340:Drug Contamination; D004355:Drug Stability; D005615:Freezing; D006207:Half-Life; D013058:Mass Spectrometry / Q000379:methods*; D008657:Metabolic Clearance Rate; D009153:Mutagens / Q000032:analysis; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D012680:Sensitivity and Specificity; D013431:Sulfates / Q000032:analysis*; D013997:Time Factors
D000476:Alkanesulfonates; D009153:Mutagens; D004364:Pharmaceutical Preparations; D013431:Sulfates