Ichikawa N, Naora K, Hirano H, Iwamoto K
Department of Pharmacy, Shimane Medical University Hospital, Japan.
J Pharm Biomed Anal. 1998 Sep;17(8):1415-21. doi: 10.1016/s0731-7085(98)00024-7.
A simple and sensitive high-performance liquid chromatographic method for the analysis of acetazolamide (AZ) in rat blood (plasma/serum, whole blood and serum ultrafiltrate), brain tissue and cerebrospinal fluid (CSF) was described. Quantitative extraction of AZ with ethyl acetate from both buffered plasma and brain tissue homogenate (pH 8.0) was achieved. Each extract was evaporated to dryness and the residue was chromatographed on a reversed-phase column. CSF was directly analysed without extraction step. The limits of detection were 0.05 microgram ml-1 for plasma, 0.02 microgram g-1 for brain tissue and 0.004 microgram ml-1 for CSF. Calibration curves were linear over the working ranges of 0.1-100 micrograms ml-1 for plasma, 0.05-50 micrograms g-1 for brain tissue and 0.025-50 micrograms ml-1 for CSF. The reproducibility of AZ assay in the rat biologic media indicated very low relative standard deviations (RSDs). The recoveries of AZ added to plasma and brain tissue were more than 96% with an RSD of less than 5%. The present method was applied to studies of plasma concentration profiles of the drug after administration and its distribution into central nervous system.
描述了一种简单、灵敏的高效液相色谱法，用于分析大鼠血液（血浆/血清、全血和血清超滤液）、脑组织和脑脊液（CSF）中的乙酰唑胺（AZ）。用乙酸乙酯从缓冲血浆和脑组织匀浆（pH 8.0）中定量提取AZ。将各提取物蒸发至干，残渣在反相柱上进行色谱分析。脑脊液无需提取步骤即可直接分析。血浆的检测限为0.05微克/毫升，脑组织的检测限为0.02微克/克，脑脊液的检测限为0.004微克/毫升。血浆在0.1 - 100微克/毫升、脑组织在0.05 - 50微克/克、脑脊液在0.025 - 50微克/毫升的工作范围内校准曲线呈线性。AZ在大鼠生物介质中的测定重现性表明相对标准偏差（RSD）非常低。添加到血浆和脑组织中的AZ回收率超过96%，RSD小于5%。本方法应用于给药后药物血浆浓度曲线及其在中枢神经系统分布的研究。
