To study the systemic exposure of tazarotene formulation after topical administration, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of tazarotene and tazarotenic acid in minipig plasma. Similar extraction recoveries for both analytes were obtained after the plasma samples were acidified by glacial acetic acid (5%) and extracted by ethyl ether-cyclohexane (4:1, v/v). Separation of the analytes was achieved within a short time by the addition of 0.1% formic acid to the mobile phase. Gradient elution was used to avoid the matrix effect. The method was linear over the concentration range of 10-600 pg/mL for both analytes. The data of intra- and inter-run precision and accuracy were lower than 5.2%, 7.3% and 7.3% for both analytes. The developed method can be applied to investigate the transdermal pharmacokinetics and the systemic exposure of tazarotene formulation after topical administration.