Abstract: Ambroxol and clenbuterol were extracted from human plasma samples by liquid-liquid extraction, ambroxol was separated on a Zorbax XDB-C₁₈ column and detected by tandem mass spectrometry with an atmospheric pressure chemical ionization interface after oral administration of a compound preparation. Clenbuterol was separated on a Zorbax XDB-C₈ column and detected by tandem mass spectrometry with an electrospray ionization interface. Diphenhydramine is used as the internal standard. The linear concentration ranges of the calibration curves for ambroxol and clenbuterol were 0.080-400 μg·L^-1 and 5.0-5 000 ng·L^-1, respectively. The lower limits of quantification were 0.080 μg·L^-1 for ambroxol and 5.0 ng·L^-1 for clenbuterol, individually. The inter-day and intra-day precision (RSD) across three validation run over the entire concentration range was below 7.5%, and the accuracy (RE) was within ±2.5% for both ambroxol and clenbuterol. The methods were used to determine the pharmacokinetic parameters of ambroxol and clenbuterol in human plasma after oral administration of a compound preparation containing 60 mg ambroxol hydrochloride and 40 μg clenbuterol hydrochloride. The method was proved to be highly sensitive, selective and suitable for the pharmacokinetic study of different compound preparations containing ambroxol and clenbuterol.