The two people said Runge failed at least one drug test, then reached an agreement so he could remain on the umpire roster. When he failed to comply with those terms, he was released.
The people spoke on condition of anonymity because MLB didn't publicly say why Runge was gone.
It could not be independently determined by the AP what drug was involved.
Joe West, president of the World Umpires Association the union representing umps declined comment Tuesday.
The AP was unable to contact Runge through the union or other umpires.
Like players, umpires are subject to random drug tests. Oakland pitcher Bartolo Colon, Philadelphia catcher Carlos Ruiz and San Diego catcher Yasmani Grandal all missed time this season because of drug suspensions imposed last year. In addition, 26 players have been suspended this year under the minor league drug program.
The 43-year-old Runge didn't work in the majors after last Aug. 30 while dealing with a knee injury. He called spring training games this year and later did several Triple-A games, but hadn't been back in the big leagues during the regular season.
Runge joined the MLB umpiring staff in 1999. He worked playoffs three times and last year's All-Star game.
He is a member of MLB's first three-generation family of umpires. Grandfather Ed was an American League umpire from 1954-70 and worked the World Series three times; father Paul called National League games from 1973-97 and did the World Series four times before becoming the NL's executive director of umpires.
Brian Runge was behind the plate for a pair of no-hitters last year Philip Humber's perfect game and the combo effort by six Seattle pitchers. He also was at third base for Matt Cain's perfect game last season.
Chris Conroy was promoted from Triple-A last month to take Runge's spot on the MLB umpiring staff. Conroy had worked 267 regular-season games in the majors as a fill-in since 2010 before being hired permanently.