No abstract

Aztreonam (SQ 26,776) is a new synthetic monocyclic P-lactam antibiotic which is specifically active against aerobic gram-negative bacteria. High-pressure liquid chromatographic (HPLC) systems were developed for the quantitative analysis of aztreonam in human, monkey, rat, mouse, and rabbit sera and urine. The HPLC conditions employed for these analyses were a ,uBondapak C18 column, a mobile phase made up of 0.005 M tetrabutylammonium hydrogen sulfate at pH 3.0 and acetonitrile or methanol, UV detection at 293 nm, and a flow rate of 2.0 ml/min. For human sera and urine, the mobile phase was 80%o 0.005 M tetrabutylammonium hydrogen sulfate-0.005M (NH4) 2SO4 and 20% acetonitrile (vol/vol). For the range of sera and urine, HPLC analyses were shown to have excellent detector linearity of aztreonam over a concentration range of 1.0 mg/ml to 0.5 ,ug/ml. Correlation coefficients for plots of aztreonam peak area versus its concentration were -0.990. The detection limit of aztreonam was 1.0 jig/ml in sera and 5.0 ,ug/ml in urine. HPLC and microbiological assays of aztreonam in human sera and urine were in good agreement.Aztreonam (SQ 26,776) (Fig. 1) is a totally synthetic monocyclic ,-lactam antibiotic specifically active against aerobic gram-negative bacteria (6). It is a member of the monobactams, naturally occurring 3-lactams produced by bacteria (7). This compound is currently undergoing clinical development, and human pharmacology data have been reported in detail (4,5).The assay of antibiotics in body fluids has traditionally been performed by microbiological assay, but recently high-pressure liquid chromatography (HPLC) has been extensively employed as an alternative procedure (8,11 3.9 mm; length, 3.0 cm). The guard column was packed with Bondapak C18 on Corasil. For studies with both chromatographic systems, the following conditions were employed: a UV detector setting of 293 nm, a solvent flow rate of 2.0 ml/min, and a chart speed of 0.5 cm/min. Quantitation of aztreonam was performed by an external standard method of calculation, and peak area measurements were used.Aztreonam. Aztreonam, prepared in our laboratories, was used as either the dipolar ion form shown in Fig. 1 or the disodium or dipotassium salt formed from the free diacid.