If it's not one of the issues 3alarmer raises, then a new Ultegra QR will likely solve your issue. A properly installed internal cam quick release should not slip in horizontal dropouts.
Since you mention 42x16 I assume are running a fixed gear. A lower gear is actually putting more torque on the wheel.

If you're just a monster of 275 lbs of solid muscle or something, there's always track hubs with nuts and solid axles.