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-amino-benzoic 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 × 150 mm column with acetonitrile-0.1 mol/1 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 μg/ml in human plasma. The linear quantification range of the method was 0.1 ∼ 50 μg/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.

Key words

Antibacterial - Biapenem - CAS 120410-24-4 - Human plasma and urine - Pharmacokinetics - RP-HPLC

• References

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