Determination of bis(tributyltin) oxide by GC--MS with on-line hydride derivatization: application to drug substance analysis.

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.