Lakings D B, Wozniak J M
J Chromatogr. 1984 Jun 8;308:261-71. doi: 10.1016/s0021-9673(01)87552-x.
Quantitative analytical methods have been defined for the determination of cefpimizole, a new broad-spectrum cephalosporin antibiotic, in plasma and urine specimens. The methods employ ion-pair reversed-phase high-performance liquid chromatography with both ethylene-diaminetetraacetic acid (EDTA) and tetrabutylammonium hydroxide as pairing agents for separation and ultraviolet detection at 254 nm. Sample preparation for plasma aliquots consisted of acetonitrile protein precipitation followed by phase separation; the aqueous phase was filtered and assayed. For urine, sample preparation consisted of diluting an aliquot with chromatographic eluent, filtering, and assaying. The methods had a linear range of 17-0.3 micrograms/ml for plasma and 800-15 micrograms/ml for urine and had sufficient precision and accuracy to provide quantitative data. Stability studies in plasma and urine indicated that cefpimizole degraded rapidly at room temperature. Addition of EDTA to the physiological fluid substantially increased the stability at room temperature, and little or no degradation was observed in plasma or urine stored at -30 degrees C for over 100 days. Utility of the methods was demonstrated by assaying plasma and urine specimens obtained from a human volunteer receiving three dose levels. Estimates of various pharmacokinetic parameters are presented.
已定义了定量分析方法，用于测定血浆和尿液样本中的头孢咪唑（一种新型广谱头孢菌素抗生素）。这些方法采用离子对反相高效液相色谱法，以乙二胺四乙酸（EDTA）和氢氧化四丁铵作为配对剂进行分离，并在254nm处进行紫外检测。血浆等分试样的样品制备包括用乙腈进行蛋白沉淀，然后进行相分离；水相经过过滤后进行分析。对于尿液，样品制备包括用色谱洗脱液稀释一份试样、过滤并进行分析。这些方法对于血浆的线性范围为17 - 0.3微克/毫升，对于尿液为800 - 15微克/毫升，并且具有足够的精密度和准确度以提供定量数据。血浆和尿液中的稳定性研究表明，头孢咪唑在室温下迅速降解。在生理流体中添加EDTA可显著提高其在室温下的稳定性，并且在-30℃下储存超过100天的血浆或尿液中几乎没有观察到降解。通过分析从接受三个剂量水平的人类志愿者获得的血浆和尿液样本，证明了这些方法的实用性。给出了各种药代动力学参数的估计值。
