An ultraperformance liquid chromatography-tandem mass spectrometry method for determination of anastrozole in human plasma and its application to a pharmacokinetic study.

A fast, selective and sensitive ultraperformance liquid chromatography-tandem mass spectrometry method was developed for determination and pharmacokinetic study of anastrozole in human plasma. Plasma sample pretreatment involved a one-step extraction with diethyl ether of 500 µL plasma. The chromatographic separation was carried out on an Acquity UPLC(TM) BEH C(18) column with a mobile phase consisting of methanol-10  mmol/L ammonium acetate (75:25, v/v) at a flow rate of 0.30 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring via electrospray ionization source with positive mode. A high throughput was achieved with a run time of 1.5 min per sample. The standard curve for anastrozole was linear (r(2) ≥ 0.99) over the concentration range of 0.0550-27.5 ng/mL with a lower limit of quantification of 0.0550 ng/mL. The intra- and inter-day precision (relative standard deviation) values were not higher than 14% and the accuracy (relative error) was within ±3.2% at three quality control levels. This simple, fast and highly sensitive method was fully validated and successfully applied to a clinical pharmacokinetic study of anastrozole in healthy volunteers after oral administration.