DETERMINATION OF LEVOFLOXACIN IN PLASMA AND CEREBROSPINAL FLUID WITH HPLC AND ITS PHARMACOKINETICS IN PATIENTS UNDERGOING NEUROSURGICAL OPERATIONS

A RP-HPLC method was developed to determine the concentrations of levofloxacin in plasma and cerebrospinal fluid and its pharmacokinetics were studied in patients undergoing neurosurgical operations. C₁₈H₃₇ column was eluted with the mobile phase consisting of 10 mmol·L^-1 KH₂PO₄-10 mmol·L^-1 (C₄H₉)4Br-CH₃CN(45∶45∶10, pH 3.0) and the utraviolet absorbance was monitored at 295 nm. Ciprofloxacin was used as internal standard. The mean recoveries were 74.76% in plasma and 82.43% in cerebrospinal fluid, with the lowest detectable limits of 10 μg·L^-1 and 6μg·L^-1, respectively. The RSD for the intraday and inter-day were all less than 5%.A single oral administration of 300 mg levofloxacin tablet was given to 10 patients undergoing neurosurgical operations. The pharmacokinetic parameters in blood and in cerebrospinal fluid could be described by one compartment open model. The pharmacokinetic parameters were: blood Ke 0.12±0.04 h^-1, T_1/2 6.05±1.68 h, T_max 1.05±0.29 h, C_max 3.67±0.42 mg·L^-1, AUC 33.43±7.32 mg·h·L^-1, CLs 9.46±2.53 L·h^-1, Vd 77.49±7.39 L; cerebrospinal fluid Ke 0.11±0.04 h^-1, T_1/2 6.95±1.88 h, T_max 3.56±1.24 h, C_max 1.68±0.25 mg·L^-1, AUC 23.70±5.62 mg·h·L^-1, CLs 13.70±5.11 L·h^-1, Vd 126.61±13.20 L.