TMA-230

The authors demonstrate that three new carbapenems (BO-2727, DX-8739, S-4661) and one new penem (AMA-3176) are relatively stable to human recombinant dehydropeptidase-I in vitro.The rank order of the stability against hydrolysis by the enzyme was: BO-2727 > AMA-3176 > S-4661 > DX-8739 >> imipenem.The next steps will be to determine the in vivo stability of the antibiotics and to evaluate their clin. usefulness.

Various penems, structurally closely related carbapenems, and the intermediate 4‐acetoxyazetidin‐2‐one were studied by direct current sampled dc, differential pulse polarography (DPP), cyclic voltammetry, and ac tensammetry. Optimum pH ranges for the determination of 4‐acetoxyazetidin‐2‐one and the various penems are discussed. In Britton—Robinson buffer (BRP) penems exhibit (pH 3) one stable reduction wave, which can be exploited analytically. Carbapenems exhibit stability problems in BRP (pH 3). They can be determined after conversion by hydrolysis into a stable imine form. Useful linear concentration ranges are 10 to 140 μg/mL for 4‐acetoxyazetidin‐2‐one and 20 to 170 and 0.5 to 70 μg/mL for penems using dc polarography and DPP, respectively. The precision of the proposed analytical methods is acceptable, with relative standard deviations around 2.5% for the assay of 4‐acetoxyazetidin‐2‐one and 2.5 and 2–5% for the penem and carbapenem, respectively.