title: Determination of bis(tributyltin) oxide by GC--MS with on-line hydride derivatization: application to drug substance analysis.
abstract: We report the determination of residual bis(tributyltin) oxide in a drug substance by GC-MS after extraction and on-line conversion to tributyltin hydride. Gas chromatography was performed using a 15 m x 0.25 mm i.d. DB-5 HT column with a temperature program from 100 to 160 degrees C at 15 degrees C min(-1). A mass range of 165-185 amu was monitored with the MS detector. Hydride generation is performed by placing a small amount of solid sodium borohydride in the injection port of a gas chromatograph and injecting samples and standards through this material. Conversion to tributyltin hydride is shown to be quantitative and linear for levels of bis(tributyltin) oxide between 1 and 100 ppm in the drug substance. The use of GC-MS provides sensitive and selective detection of tin containing species and the tin isotope pattern allows for confirmation of the presence of tin in chromatographic peaks. Recovery at 6 ppm was 89% with an injection precision of 6%. The limit of detection for bis(tributyltin) oxide in drug substance is 1 ppm.
authors.affiliation: Merck Research Laboratories, Rahway, NJ 07065-0914, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: O'Brien
authors.forename: T M
authors.initials: TM
authors.lastname: Dowling
authors.forename: C W
authors.initials: CW
authors.lastname: Moeder
authors.forename: G R
authors.initials: GR
authors.lastname: Bicker
mesh_terms: D001894:Borohydrides / Q000737:chemistry*; D004340:Drug Contamination / Q000517:prevention & control*; D005069:Evaluation Studies as Topic; D008401:Gas Chromatography-Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D008452:Maximum Allowable Concentration; D009947:Organotin Compounds / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014220:Trialkyltin Compounds / Q000032:analysis*
chemical_list: D001894:Borohydrides; D009947:Organotin Compounds; D004364:Pharmaceutical Preparations; D014220:Trialkyltin Compounds; C005961:bis(tri-n-butyltin)oxide; C025364:sodium borohydride