目的 探讨淋巴结结核患者血浆与淋巴结组织中异烟肼浓度的相关性,发掘其临床价值.方法 收集武汉市肺科医院淋巴结结核患者基本信息以及不同时间点静脉血液和手术切除的颈淋巴结组织样本,建立超高效液相色谱-串联质谱(UPLC-MS/MS)法并定量检测患者血浆和颈淋巴结组织样本中的异烟肼浓度,分析血浆与淋巴结组织中异烟肼浓度的相关性.结果 异烟肼血药浓度及淋巴结组织浓度的线性范围分别为 0.25~16 μg·mL-1(r=0.999 8)、2~128 μg·g-1(r=0.998 8).各质控样品的精密度、准确度、基质效应等均符合要求.血浆与淋巴结组织中的异烟肼浓度在患者静脉滴注给药后 10 min(r=0.501 1,P=0.001)、30 min(rs=0.402 8,P=0.005)和 60 min(r=0.614 6,P=0.001)均具有正相关性.对淋巴结组织与血浆中的异烟肼浓度比值进行分析,结果发现在 10,30,60 min 时该比值分别为 1.46(0.62,3.55),5.25(4.61,11.61),6.62(4.42,10.78)mL·g-1.结论 建立的UPLC-MS/MS法专属性好,灵敏度、准确度及精密度高.监测血浆异烟肼浓度可为临床淋巴结核患者合理使用异烟肼提供参考.
Objective To investigate the correlation between isoniazid concentration in plasma and lymph node tissue of patients with lymph node tuberculosis,and to explore its clinical value.Methods The basic information of patients with lymph node tuberculosis in our hospital and venous blood samples and neck lymph node tissue samples at different time points were collected.UPLC-MS/MS method was established and isoniazid concentration in plasma and neck lymph node tissue samples was quantitatively detected,and the correlation between isoniazid concentration in plasma and lymph node tissue was analyzed.Results The linear range of isoniazid blood concentration and lymph node tissue concentration were 0.25-16 μg·mL-1(r=0.999 8)and 2-128 μg·g-1(r=0.998 8),respectively.The precision,accuracy,and matrix effect of each quality control sample met the requirements.Plasma isoniazid concentration and lymph node tissue isoniazid concentration were significantly correlated at 10 min(rs=0.501 1,P=0.001),30 min(rs=0.402 8,P=0.005)and 60 min(rs=0.614 6,P=0.001)after intravenous infusion of isoniazid.The ratio of lymph node tissue isoniazid concentration to plasma isoniazid concentration was 1.46(0.62,3.55)mL·g-1 at 10 min.At 30 min,the ratio was 5.25(4.61,11.61)mL·g-1.At 60 min,the ratio was 6.62(4.42,10.78)mL·g-1.Conclusion The established UPLC-MS/MS method has good specificity,high sensitivity,accurac and precision.Monitoring plasma isoniazid concentration provides a reference for the rational use of isoniazid in patients with lymphatic tuberculosis.