Quantitative determination of salbutamol in plasma, as either its trimethylsilyl or t-butyldimethylsilyl ether, using a stable isotope multiple ion recording technique.

Abstract

Two methods are described for the determination of salbutamol in human plasma. The drug is extracted from the plasma as a salbutamol tetraphenylboron ion pair and determined by gas chromatography mass spectrometry. Trideuterio-salbutamol is used as an internal standard. In the first method an extensive purification procedure is used to separate salbutamol from plasma cholesterol which interferes in the assay. Salbutamol is then determined as its TMS-ether using a multiple ion recording technique to measure the intensity of the fragment ion m/e 369 and the ion m/e 372 from the TMS ether of trideuterio-salbutamol. The second method is based on the ion pair extraction of salbutamol into heptan-3-one and its determination by gas chromatography mass spectrometry as the t-butyldimethylsilyl ether. The base peak in the mass spectrum of the t-butyldimethylsilyl-salbutamol is an ion of m/e 495, which is of sufficiently high mass to distinguish it from any of the ions which arise from t butyldimethylsilyl-cholesterol. Six replicate analyses of plasma samples containing 1 ng salbutamol ml-1 were carried out using both methods. When the first method was used the mean value obtained was 1.3 ng ml-1 and the coefficient of variation was 17.7%. When the second method was used the mean value obtained was 0.95 ng ml-1 and the coefficient of variation was 10%. The second method is more rapid and therefore preferable for use in clinical pharmacological studies. This method has been used to determine the plasma salbutamol concentrations at varying times after either a 4 mg oral or a 200 mug intravenous dose of salbutamol to man.