Stability of beta-lactamase inhibitors and beta-lactam antibiotics in parenteral dosage forms and in body fluids and tissue homogenates: a comparative study of sulbactam, clavulanic acid, ampicillin and amoxycillin.

The beta-lactamase inhibitors and the beta-lactam antibiotics differ appreciably in chemical stability. A comparative study of four different infusion solutions at 4, 25 and 37 degrees C yielded the following descending sequence of stability: sulbactam (CAS 68373-14-8), ampicillin (CAS 69-53-4), amoxycillin (CAS 61336-70-7) and clavulanic acid (CAS 58001-44-8). Especially noteworthy was that the two beta-lactamase inhibitors, sulbactam and clavulanic acid, behaved very differently. Moreover, sulbactam is markedly more stable than clavilanic acid even when incubated at 37 degrees C in body fluids or tissue homogenates. The differences in the chemical stability of these pharmacological agents should be taken into consideration in the therapeutic use of combination preparations such as sulbactam/ampicillin (Unacid(R)) and clavulanic acid/amoxycillin.