| ObjectivesTo provide references for clinical administration, the excretion of cefathiamidine in patients with hysterectomy under lumbar-epidural anesthesia was studied. The study consists of two parts. First, a method for the determination of the cefathiamidine in urine by HPLC was developed and validated. And the second, based on urine drug method, the self-control study of renal clearance for the cefathiamidine was carried out in patients with hysterectomy under lumbar-epidural anesthesia.Methods1. The method of determination the concentrations of cefathiamidine in urine by HPLCThe chromatographic separation was performed on a Inertsil ODS column (4.6×150mm,5μm), operated at40℃. A Security Guard Cartridges C18column (4x3.0, mmPhenomenex, USA) was employed as guard column. The mobile phase, formed by acetonitrile-50mM Potassium dihydrogen phosphate buffer (18:82, v/v), was delivered with a flow rate of1mL/min, and the injection volume was20μl, the detection wavelength was254nm.2. The study of the renal clearance in patients with hysterectomy under lumbar-epidural anesthesia on the basis of urine drug method.Thirteen eligible patients with hysterectomy under lumbar-epidural anesthesia confirmed ASA grade Ⅰ-Ⅲ, and the operations were lasted about3hours. The dosing of urine were collected in0-1,1-2,2-3,3-4,4-5hours period respectively, after completion of each dosing, and saved in-80℃for determination.Eligible patients received cefathiamidine (intravenous injection,2g in1hour) twice at the beginning of the lumbar-epidural anesthesia, and8hours after the anesthesia when they came back to ward. The dosing of urine were collected as before.The method of determination the concentrations of cefathiamidine in urine.The concentrations of cefathiamidine in urine sample were determined by HPLC.Results1. The result of the determination method for the concentrations of cefathiamidine in urineLinearity was covering a concentration range from39.06to5000mg-L"1. Recoveries of cefathiamidine were96.08%95.81%and94.18for the low, middle and high solubility (78.12、625.0,4000mg·L-1), respectively. The concentrations of was measured by the corresponding standard curves, and then the precision and accuracy were calculated. The within-batch precisions were6.2%,1.2%and3.8%for the low, middle and high solubility (78.12.625.0、4000mg·L-1), and the mean of within-batch accuracy were95.3%.97.6%、97.1%separately. Between-batch precision and accuracy were obtained by3replicates at three concentration levels (78.12.625.0,4000mg·L-1). The between-batch precision and accuracy were5.4%,2.3%,3.6%and92.3%,98.0%,98.1%respectively. The RSD of the lowest concentration of level (LLOQ) was4.3%. All stability tests, including the stabilities of standard stock solution and urine samples processing fluid, short-term, long-term and freeze-thaw stability of urine samples, were performed and conformed to the relevant requirements.2. The results of pharmacokineticsThe results of pharmacokinetic parameters were calculated with the software WinNonlin6.1. The elimination half-life (t1/2β) of the early group and the second group were1.95±0.97h and1.12±0.44h respectively. A paired sample t-test was used to determine whether there was a significant difference between the two groups by SPSS17.0, which showed that the elimination half-life of cefathiamidine in the anesthesia group was longer than the group without anesthesia (p<0.05).Conclusions1. A sensitive and specific HPLC method for quantifying cefathiamidine in human urine was developed and validated.2. The elimination half-life of cefathiamidine in the anesthesia group was longer than the group without anesthesia. It shows that the body’s stress response, caused by anesthetic, medication in period of perianesthesia or surgical trauma, may affect the clearance of drugs and extend the elimination half-life of drugs. The mechanism may be related to the change of organ plasma perfusion by using perianesthesia drugs and surgical trauma. |
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