Application of dynamic laser scattering to the quality control of injectable drugs: polymer formation in ampicillin solution

OBJECTIVE: To assess the usefulness of dynamic laser scattering for monitoring the stability of ampicillin after reconstitution from commercially available vials with respect to the polymer formation and potency. METHODS: Polymer formation and the remaining potency of the reconstituted ampicillin solution were estimated using dynamic laser scattering and high-performance liquid chromatography. RESULTS: The laser light-scattering submicron particle analyser was sufficiently sensitive for detecting both monomer and polymer aggregates with the average diameter of 1.1 +/- 0.2 and 7.3 +/- 1.7 nm, respectively, in the ampicillin solution. Polymer formation was dependent on both the storage temperature and the storage period, but it was detected, even when no precipitates were visible and when loss of potency was less than 10% of the initial value following storage at 4 or -15 degrees C. CONCLUSION: Submicron particle analysis using scanning electron microscopy, when used in combination with high-performance liquid chromatography, provides a useful method for studying polymer formation in antibiotic solutions and for the quality control of antibiotic injections during storage.