HPLC法检测脊柱结核病椎内外异烟肼和乙酰异烟肼浓度

High-performance liquid chromatography for detecting the concentrations of isoniazid and acetylisoniazid in spinal tuberculosis

目的研究脊柱结核正规化疗后异烟肼及代谢产物在病椎内外分布的特点。方法23例应用3SHRE/15HRE化疗方案结合手术治疗的脊柱结核患者,术前按年龄分4组行脊柱CT检查,测量核病灶、病灶外病椎及正常椎骨CT值。化疗第4周手术,术中再取病椎各部作高效液相色谱分析(HPLC),测量抗结核药异烟肼(INH)及其代谢产物乙酰异烟肼(AC-INH)浓度。结果(1)INH和AC-INH在血液中的浓度水平最高,在正常髂骨和非硬化骨病椎中浓度次之,硬化壁和病灶中浓度极低。(2)在病椎非硬化骨中INH和AC-INH浓度与正常椎骨之间无统计学差异(P>0.05)。(3)在病椎硬化骨中INH和AC-INH浓度与正常椎骨之间有统计学差异(P<0.05)。(4)在病灶中几乎测不出该药浓度。结论INH和AC-INH在脊柱结核患者正常椎骨与非硬化骨的病椎中可达到有效治疗浓度,而在病灶及有硬化骨的病椎中难以达到有效的药物浓度。

Objective To study the distribution of isoniazid and its metabolite in spinal tuberculosis following chemotherapy.Methods Twenty-three patients with spinal tuberculosis received chemotherapy with 2SHRZ/16HRZ（for a total of 18 months）.Four weeks after the chemotherapy,all the patients underwent surgery and specimens of the serum,ilium and vertebral tissue including the sclerotic wall,focus inside the sclerotic wall（if present） and destructed foci were obtained.CT was performed in all the cases to test the HU of the foci before operation,and the levels of isoniazid and its metabolite in the specimen were measured with high-performance liquid chromatography（HPLC）.Result The levels of isoniazid and its metabolite were the highest in the serum,followed by normal ilium and non-sclerotic bone,and were extremely low in the sclerotic wall and foci.Their levels in the non-sclerotic bone of the compromised vertebra and normal vertebra showed no significant difference（P〉0.05）,but in the sclerotic bone,their levels were significantly higher than in the normal vertebra（P〈0.05）.Isoniazid and its metabolite are hardly detectable in the sclerotic foci in the compromised vertebrae.Conclusion Isoniazid and its metabolite may reach therapeutic concentration in normal vertebra and nonsclerotic bones of the compromised vertebra,but not in the disease foci or the sclerotic bone of the compromised vertebrae.