Defending champion Stefanos Tsitsipas and Daniil Medvedev were both dumped out at the quarter-final stage of the Monte Carlo Masters, with Taylor Fritz and Holger Rune advancing.

Seeded second and third respectively, Tsitsipas and Medvedev began Friday as the tournament's highest-ranked players following Novak Djokovic's shock exit, but both found themselves on the receiving end of comprehensive defeats.

World number three Tsitsipas was the victim as Fritz claimed his first victory over a top-10 ranked player on clay, ending the Greek's 12-match winning run at the competition with a 6-2 6-4 success.

Tsitsipas – who won the event in both 2021 and 2022 – was unable to contain Fritz as the American hit a series of huge winners en route to his third Masters 1000 semi-final.

Fritz will face Andrey Rublev in the final four after the fifth seed saw off the challenge of German qualifier Jan-Lennard Struff, posting a 6-1 7-6 (7-5) win.

3 - @Taylor_Fritz97 has become only the third American to reach the semi-final at the Monte Carlo Masters, since the introduction of the ATP Masters 1000 format in 1990. Vincent Spadea was the last US semi-finalist in 2003. Big.#RolexMonteCarloMasters | @atptour @ATPMediaInfo pic.twitter.com/FqwYNdc8uA

— OptaAce (@OptaAce) April 14, 2023

Meanwhile, Medvedev came up short in his tussle with Rune, as the 19-year-old waltzed into his second Masters 1000 semi-final with a 6-3 6-4 triumph.

"It wasn't easy for sure, it's always tough to play Daniil," Rune said after his win. "It was actually my first time playing against him in a real match, but we've practised tonnes of times. 

"I have huge respect for everything he's done. In the last week it was not easy to stop him, but I'm happy I managed to do it."

Rune now has a 10-8 record in meetings with his fellow top-10 players, and he will have to win another such duel to make the final, with Jannik Sinner his semi-final opponent.

Sinner needed 76 minutes to beat fellow Italian Lorenzo Musetti 6-2 6-2, and the 21-year-old now has the chance to reach his third Masters 1000 final, having previously finished as runner-up at two editions of the Miami Open.

1 - @holgerrune2003 has become the first teenager to claim multiple top-five wins in ATP Masters 1000 quarter-finals since 1990. Rune's other QF victory came against fellow teenager Carlos Alcaraz (Paris 2022). Legitimate.#RolexMonteCarloMasters | @atptour @ATPMediaInfo pic.twitter.com/WXfIgRV7lL

— OptaAce (@OptaAce) April 14, 2023