What are the causes of split albumin in serum protein electrophoresis?

A split albumin peak on serum electrophoresis is primarily caused by the binding of medications or substances to albumin, altering its electrophoretic mobility. Common medications that cause this phenomenon include beta-lactam antibiotics (particularly penicillins and cephalosporins), valproic acid, and high-dose aspirin. Other causes include the presence of bisalbuminemia (a genetic variant where two types of albumin coexist), hemolysis which releases free hemoglobin that binds to albumin, and contrast media used in radiological procedures. The split occurs because when these substances bind to albumin, they change its electrical charge, causing a portion of the albumin to migrate at a different rate during electrophoresis. This creates two distinct peaks or a shoulder on the albumin band rather than a single peak. It's important to recognize this pattern as a medication effect or variant rather than misinterpreting it as a pathological protein abnormality. The finding is generally benign and resolves when the causative medication is discontinued, though genetic bisalbuminemia will persist as it represents a hereditary condition.