A simple gas chromatographic mass spectrometric determination of the impurity 3‐quinuclidinyl benzilate in the anticholinergic agent clidinium bromide (3‐hydroxy‐1‐methylquinuclidinium bromide benzilate) is not feasible because clidinium bromide decomposes to 3‐quinuclidinyl benzilate in the injection port of the gas chromatograph; the trimethylsilyl derivative of clidinium bromide also decomposes to the trimethylsilyl derivative of 3‐quinuclidinyl benzilate. Therefore, a quantitative thin‐layer chromatographic gas chromatographic mass spectrometric method has been developed for determining 3‐quinuclidinyl benzilate in clidinium bromide, using β‐piperidylethyl benzilate as an internal standard. A band containing only 3‐quinuclidinyl benzilate and β‐piperidylethyl benzilate can be eluted from the thin‐layer chromatographic plate. The samples are analyzed by single ion monitoring of m/z 255 produced by the trimethylsilyl derivatives of 3‐quinuclidinyl benzilate and β‐piperidylethyl benzilate which are separated by gas chromatography. A level of 0.03% of 3‐quinuclidinyl benzilate can be determined with a precision of about 6%; the lower limit of detection of 3‐quinuclidinyl benzilate alone is about 1 ng on the thin‐layer chromatographic plate. Analysis of a reference standard of clidinium bromide by the thin‐layer chromatographic gas chromatographic mass spectrometric procedure showed that it contained no detectable 3‐quinuclidinyl benzilate. One commercial bulk sample of clidinium bromide contained about 0.018% of 3‐quinuclidinyl benzilate, while a formulated sample of clidinium bromide contained no detectable 3‐quinuclidinyl benzilate. Commercial samples of clidinium bromide containing chlordiazepoxide can be analyzed for 3‐quinuclidinyl benzilate only with difficulty using this method. Copyright © 1979 Heyden & Son Ltd
