Stability of amoxicillin-clavulanate in BACTEC medium determined by high-performance liquid chromatography and bioassay.
The stabilities of amoxicillin (16 micrograms/ml) and clavulanate (8 micrograms/ml), alone and in combination in BACTEC medium (Middlebrook 7H12B medium), were determined by high-performance liquid chromatography (HPLC) and bioassay. By HPLC, the half-life of amoxicillin (trihydrate and sodium) in combination with clavulanate in nonradiolabelled 7H12B medium was 6.7 days, whereas the half-life of clavulanate in combination with amoxicillin was 2.0 days. By bioassay, the half-lives of amoxicillin trihydrate and clavulanate in radiolabelled 7H12B medium were comparable (7 and 2 days, respectively) to those determined by HPLC. When clavulanate was tested alone, the half-life was determined to be 1.88 days by HPLC and 1.87 days by bioassay. The relatively short half-life of clavulanate can be adjusted by a procedure of "topping up," or adding one-half the concentration of clavulanate every second day, in order to allow accurate amoxicillin-clavulanate MIC testing with the BACTEC mycobacterial susceptibility system.
Moore
T D
TD
SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
Horton
R
R
Utrup
L J
LJ
Miller
L A
LA
Poupard
J A
JA
D000658:Amoxicillin / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D019980:Amoxicillin-Potassium Clavulanate Combination; D001681:Biological Assay; D002851:Chromatography, High Pressure Liquid; D002969:Clavulanic Acids / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D003470:Culture Media; D004355:Drug Stability; D004359:Drug Therapy, Combination / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D006207:Half-Life; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects / Q000254:growth & development
D002969:Clavulanic Acids; D003470:Culture Media; D019980:Amoxicillin-Potassium Clavulanate Combination; D000658:Amoxicillin