SHR110008 is a representative 9-β-dihydro-9,10-O-acetal taxane with greater anticancer activity and less toxicity than docetaxel. To support a preclinical study of its pharmacokinetics and to predict the effect of 9-β-dihydro-9,10-O-acetal modification on its pharmacokinetic properties, we have developed a sensitive and rapid liquid chromatographic–tandem mass spectrometric method for quantitative analysis of SHR110008 in rat and dog plasma. Plasma was extracted with ethyl acetate. The analytes were separated on a 150 × 4.6 mm i.d., 5 μm particle, reversed-phase C18 column with 90:10 (v/v) methanol–0.1% formic acid as mobile phase at a flow rate of 0.3 mL min−1. Detection was performed by triple-quadrupole tandem mass spectrometry in selected reaction monitoring (SRM) mode with an electrospray ionization source. The precursor-to-product ion transition m/z 933 → 142 was used. The method was validated for accuracy and precision, and linearity in the two matrices was good. Lower limits of quantification (LLOQ) in rat and dog plasma were 5 and 2 ng mL−1, respectively. There were no stability-related problems in the procedure for analysis of SHR110008. The method was successfully used in a preclinical study of the pharmacokinetics of SHR110008 in rats and beagle dogs. The pharmacokinetics of SHR110008 were non-linear in rats and dogs. The elimination half-life ranged from 5.18 to 7.32 h for the rats and from 6.42 to 8.42 h for the dogs.
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