Top seed Sara Errani bowed out of the New Haven Open after being comprehensively beaten by Ekaterina Makarova.
The seeded players have found the going tough in Connecticut all week and that was certainly the case for world No 5 Errani who went down in straight sets.
Having edged a hard-fought first set, Makarova romped through the second to complete a 7-5 6-1 triumph in one hour and 22 minutes.
Makarova of Russia will now face Romania's Simona Halep who, despite dropping her first set of the tournament, overcame Spain's Carla Suarez Navarro 3-6 6-4 6-1.
Fourth seed Caroline Wozniacki did buck the trend, however, as she produced some solid tennis to book her spot in the last eight.
The Dane, a New Haven specialist bidding for her fifth title in six years at the event, saw off Karin Knapp 6-1 7-5 to maintain her excellent record at the tournament.
Petra Kvitova, the third seed, survived a scare as she saw off the challenge of Alison Riske 7-6 (7-5) 4-6 6-3, while sixth-seeded Sloane Stephens was also taken to three sets.
Stephens finally overcame Julia Goerges 7-5 2-6 6-1.