title: Improved RP-HPLC method to determine biapenem in human plasma/urine and its application to a pharmacokinetic study.
abstract: Existing methods to determine biapenem (CAS 120410-24-4), a carbapenem, either lacked sensitivity/reproducibility or had no internal standard as a control. Here an improved reversed-phase high-performance liquid chromatographic (RP-HPLC) method was established in human plasma and urine. After adding p-aminobenzoic acid as the internal standard to plasma or urine, plasma samples were ultra-filtrated and urine samples were diluted directly. Chromatographic separations were carried out on a 4.6 mm x 150 mm column with acetonitrile-0.1 mol/l sodium acetate (2:98, v:v; pH 4.38 or 4.00) as mobile phase and UV detection at 300 nm. The extraction recovery was 91.51% for biapenem at the concentration level of 5 microg /ml in human plasma. The linear quantification range of the method was 0.1 to approximately 50 microg /ml for plasma and urine, with linear correlation coefficients greater than 0.998. The intra-day and inter-day relative standard deviations (R.S.D.) for biapenem at low, middle and high levels in human samples were less than 12.51% for plasma and less than 7.05% for urine. The RP-HPLC method was successfully applied to pharmacokinetic studies, in which healthy subjects received multiple doses of biapenem (300 mg, i.v., b.i.d., for 5 continuous days). The pharmacokinetic results are presented.
authors.affiliation: Department of Pharmacy, Beijing University People's Hospital, Beijing, P. R. China.
authors.forename: Libo
authors.initials: L
authors.lastname: Zhao
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Kou
authors.forename: Aidijie
authors.initials: A
authors.lastname: Bayasi
authors.forename: Huan
authors.initials: H
authors.lastname: Cai
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D005260:Female; D006207:Half-Life; D006801:Humans; D007202:Indicators and Reagents; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D019999:Pharmaceutical Solutions; D012015:Reference Standards; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D013845:Thienamycins / Q000032:analysis* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D007202:Indicators and Reagents; D019999:Pharmaceutical Solutions; D013845:Thienamycins; C065257:biapenem