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Aminoglycosides and penicillins chemically interact when they are combined in vitro or in vivo. The resulting adducts are considered to be biologically inactive. The major adducts formed in he interaction between tobramycin and ticarcillin have been recently isolated in pure form in our laboratory. On the basis of mass, infrared, and proton magnetic resonance spectra, the major adducts appeared 10 be amides formed by an attack of the beta-lactam carbonyl group of ticarcillin by an amino group of tobramycin. All other moieties of ticarcillin were intact except that the beta-lactam ring was opened and was rotated by 120-130 degrees . The minimum inhibitory concentrations (MICs) of the adducts, tobramycin, and ticarcillin were 20.0, 0.25, and 2.0 microg/mL for Staphylococcus aureus and Escherichia coli, and 160.0, 0.5, and 8.0 microg/mL for Pseudomonas aeruginosa. Thus, the major adducts possessed some antimicrobial activity, but not enough to be active in the treatment of infections. As shown by fluorescence polarization immunoassay (FPIA), the adducts demonstrate some cross-reactivity in the assay of tobramycin. However, it was insufficient to cause significant error in the measurement of tobramycin in human serum.

Aminoglycosides and penicillins chemically interact when they are combined in vitro or in vivo. The resulting adducts are considered to be biologically inactive. The major adducts formed in he interaction between tobramycin and ticarcillin have been recently isolated in pure form in our laboratory. On the basis of mass, infrared, and proton magnetic resonance spectra, the major adducts appeared 10 be amides formed by an attack of the beta-lactam carbonyl group of ticarcillin by an amino group of tobramycin. All other moieties of ticarcillin were intact except that the beta-lactam ring was opened and was rotated by 120-130 degrees . The minimum inhibitory concentrations (MICs) of the adducts, tobramycin, and ticarcillin were 20.0, 0.25, and 2.0 microg/mL for Staphylococcus aureus and Escherichia coli, and 160.0, 0.5, and 8.0 microg/mL for Pseudomonas aeruginosa. Thus, the major adducts possessed some antimicrobial activity, but not enough to be active in the treatment of infections. As shown by fluorescence polarization immunoassay (FPIA), the adducts demonstrate some cross-reactivity in the assay of tobramycin. However, it was insufficient to cause significant error in the measurement of tobramycin in human serum.

Failure of purification of nitrated phenylvaleric acid reaction mixtures by conventional recrystallization and column chromatographic methods using silica gel, led to a trial of counter-current chromatography. Poor solubility of the nitration products precluded the use for aqueous systems and let to the examination of systems using ethylene glycol or formamide as the stationary phase, with chloroform and other solvents as mobile phases. Prospective solvent pairs were first screened by a micropartitioning method and then by counter-current chromatography in an analytical micro counter-current chromatograph. Partition coefficients derived from these methods facilitated optimization of the solvent system and scale-up to a preparative counter-current chromatography range. Using the system chloroform-ethylene glycol, crude product was readily purified and then identified as 5-(2,4-dinitrophenyl)valeric acid. Purification using a 292-ml column provided high resolution and required 6 h. Purification with lower resolution on a 56-ml column required 2 h.