目的 建立同时测定人血清、脑脊液、胰液中利奈唑胺药物浓度的HPLC测定方法。方法 以利培酮为内标物,在0.1 mol·L^-1NaOH碱性条件下甲基叔丁基醚-正丙醇=90∶10(V/V)液液提取,Shima-pack CLC-ODS-C₁₈(6.0 mm×150 mm,5 μm)色谱柱分离,流动相为甲醇-乙腈-磷酸缓冲溶液(0.02 mol·L^-1KH₂PO₄,H₃PO₄调pH 3.5)=20∶16∶64(V/V/V),流速1.0 mL·min^-1,柱温35 ℃,检测波长254 nm条件下测定。结果 血清中利奈唑胺在0.25~40.0 mg·L^-1内线性良好(r=0.999 9),3个浓度质控样本(0.8、8.0、25.0 mg·L^-1)的批内、批间变异(RSD)分别为1.64%~2.38%(n=5)、4.53%~6.34%(n=5),方法学和提取回收率分别为93.781%~97.393%(n=5)、72.318%~73.442%(n=5);脑脊液中在0.1~20.0 mg·L^-1内线性良好(r=0.999 3),3个浓度质控样本(0.2、2.0、15.0 mg·L^-1)的批内、批间变异(RSD)分别为3.84%~4.83%(n=5)、6.04%~8.16%(n=5),方法学和提取回收率分别为106.910%~110.971%(n=5)、73.226%~80.603%(n=5);胰液中在0.1~20.0 mg·L^-1内线性良好(r=0.999 4),3个浓度质控样本(0.2、2.0、15.0 mg·L^-1)的批内、批间变异(RSD)分别为2.96%~5.30%(n=5)、4.68%~6.40%(n=5),方法学和提取回收率分别为97.178%~105.072%(n=5)、73.333%~76.010%(n=5)。内标提取回收率＞87%。结论 本方法灵敏度高,准确性好,简便快捷,应用液液提取处理样本去除更多杂峰干扰,更广泛适用于临床,尤其适用于合并用药患者生物标本中利奈唑胺药物浓度的测定。

OBJECTIVE To develop a high-performance liquid chromatographic (HPLC) method for determination of linezolid in human serum, cerebrospinal fluid (CSF) and pancreatic juice. METHODS With risperidone as internal standard, samples were extracted by methyl tert-butyl ether-n-propanol=90∶10 (V/V) after added 0.1 mol·L^-1NaOH, then seperated on a Shima-pack CLC-ODS-C₁₈(6.0 mm×150 mm, 5 μm) column with mobile phase consisted of methanol-acetonitrile-phosphate buffer solution (0.02 mol·L^-1 KH₂PO₄, pH value was adjusted to about 3.5 by H₃PO₄)=20∶16∶64(V/V/V) with a flow rate of 1.0 mL·min^-1 at 35 ℃. The detection wavelength was set at 254 nm. RESULTS For serum, the linear range of linezolid was from 0.25 to 40.0 mg·L^-1(r=0.999 9). For the three check samples(0.8, 8.0, 25.0 mg·L^-1): the intra-run and inter-run RSDs were 1.64%-2.38% (n=5) and 4.53%~6.34% (n=5) respectively, the mean method recoveries and extraction recoveries were 93.781%-97.393%(n=5) and 72.318%-73.442% (n=5) respectively. For cerebrospinal fluid, the linear range of linezolid was from 0.1 to 20.0 mg·L^-1(r=0.999 3). For the three check samples(0.2, 2.0, 15.0 mg·L^-1): the intra-run and inter-run RSDs were 3.84%-4.83% (n=5) and 6.04%-8.16% (n=5) respectively, the mean method recoveries and extraction recoveries were 106.910%-110.971% (n=5) and 73.226%-80.603% (n=5) respectively. For pancreatic juice, the linear range of linezolid was from 0.1 to 20.0 mg·L^-1(r=0.999 4).For the three check samples(0.2, 2.0, 15.0 mg·L^-1): the intra-run and inter-run RSDs were 2.96%-5.30%(n=5) and 4.68%-6.40%(n=5) respectively, the mean method recoveries and extraction recoveries were 97.178%-105.072%(n=5) and 73.333%-76.010%(n=5) respectively. The mean extraction recoveries of IS were more than 87.00%. CONCLUSION The method is sensitive, simple and accuracy, and it can be used for clinical study, espicially used in the patient with drug combination.