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The sulfate and methanesulfonate salts of polymyxin B and colistin exhibited important pharmacologic differences. The sulfate salts disappeared from plasma at a slower rate following intramuscular administration, were excreted at a much slower rate in the urine and showed a far greater calculated volume percent distribution. It is felt that these differences can be explained largely on the basis of their far greater degree of binding to plasma proteins and tissues. Evidence is presented that colistin is metabolized by the dog and that the site of metabolism may be the kidney. Renal clearance studies indicate that glomerular filtration is the mechanism of urinary excretion of colistin methanesulfonate.

A multiresidue analytical method was developed for the simultaneous determination of amoxicillin, cephapirin, procaine penicillin G, ampicil-lin, cloxacillin, and ceftiofur in bovine milk. The method involved ultrafiltration of milk diluted with an equal volume of 50% acetonitrile through a 10 000 dalton molecular mass cutoff filter. Separation of these β-lactam antibiotics from other milk components was performed by ion-paired (octane- and dodecanesulfonate) liquid chromatography using a phenyl column eluted with acetonitrile-water solution. Ultraviolet ab-sorbance of the column effluent was monitored in the 200-350 nm range of a photodiode-array detector. For quantitation, the chromatograms were acquired at λ210 nm for penicillin G, am-picillin, and cloxacillin; λ230 nm for amoxicillin; and λ290 for cephapirin, procaine, and ceftiofur. The limit of detection for the simultaneous determination of these antibiotics was estimated to be 100 ppb. Liquid chromatography/electrospray mass spectrometry could be used to confirm these antibiotics for quantities down to 100 pg entering the mass spectrometer.