Mifepristone　(RU486)　is　developed　originally　as　a　contraceptive　used　by　hundreds　of　millions　of　women　world-wide,　and　also　reported　as　a　safe　and　long-term　psychotic　depressant,　or　as　a　cancer　chemotherapeutic　agent　used　by　both　sexes.　In　our　preliminary　study　aimed　at　developing　mifepristone　as　a　cancer　metastatic　chemopreventive,　we　coincidentally　observed　that　blood　mifepristone　concentrations　in　female　rats　seem　to　be　higher　than　those　in　male　ones　post　administration.　To　substantiate　if　the　pharmacokinetic　differences　between　sexes　exist,　we　established　a　fast　UPLC-MS/MS　method　to　determine　mifepristone　concentrations　in　plasma,　and　analyzed　blood　concentrations　of　mifepristone　over　time　in　rats　and　dogs　of　both　sexes.　Mifepristone　in　plasma　or　incubation　liquid　was　recovered　by　liquid-liquid　extraction　using　1　mL　of　ethyl　acetate.　Chromatographic　separation　was　performed　on　a　C-18　column　at　35　degrees　C,　with　a　gradient　elution　consisting　of　methanol　and　water　containing　0.1%　(v/v)　formic　acid　at　a　flow　rate　of　0.3　mL/min.　And　pharmacokinetic　parameters　such　as　elimination　half-life,　and　mean　residence　time　were　calculated　by　using　the　non-compartmental　pharmacokinetics　data　analysis　software.　In　this　work,　administrations　of　mifepristone　to　rats　and　beagle　dogs　revealed　that　the　plasma　concentrations　of　mifepristone　(AUC,　C-max)　were　significantly　higher　(P　＜　0.05)　in　females　than　that　in　males.　In　vitro　liver　microsomal　incubation　experiments　showed　that　the　metabolic　rate　of　mifepristone　in　males　was　higher　than　that　in　females,　which　was　consistent　with　the　results　of　in　vivo　experiments.　In　general,　we　first　found　the　sex-related　differences　about　pharmacokinetic　properties　of　mifepristone　and　revealed　the　metabolism　difference　of　hepatic　microsomal　enzyme　is　the　main　reason.　(C)　2018　Elsevier　B.V.　All　rights　reserved.