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

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 19; no. 3; pp. 327 - 333
• Main Authors: O'Brien, Thomas P, Dowling, Thomas M, Moeder, Charles W, Bicker, Gary R
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.03.1999; Elsevier Science
• Subjects: Analysis; Biological and medical sciences; Borohydrides - chemistry; Determination of bis(tributyltin) oxide; Drug Contamination - prevention & control; Evaluation Studies as Topic; Gas Chromatography-Mass Spectrometry - instrumentation; Gas Chromatography-Mass Spectrometry - methods; GC–MS determination of tributyltin; General pharmacology; Maximum Allowable Concentration; Medical sciences; On-line hydride derivatization; Organotin Compounds - analysis; Pesticides, fertilizers and other agrochemicals toxicology; Pharmaceutical Preparations - chemistry; Pharmacology. Drug treatments; Reproducibility of Results; Selective-ion monitoring; Sensitivity and Specificity; Toxicology; Trialkyltin Compounds - analysis; Tributyltin chloride; Tributyltin hydride; Selective-ion monitoring; Tributyltin chloride; On-line hydride derivatization; Tributyltin hydride; GC–MS determination of tributyltin; Determination of bis(tributyltin) oxide; Drug; Alkylthio complex; Pesticides; Selectivity; Derivatization; In vitro; Gas chromatography; Sensitivity; Toxicology; Residue; Detection limit; Poison; Mass spectrometry; Quantitative analysis
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/S0731-7085(98)00125-3

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×0.25 mm i.d. DB-5 HT column with a temperature program from 100 to 160°C at 15°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.