液相色谱串联质谱法检测抗结核药物血药浓度情况的临床分析

Analysis of clinical results of blood concentration detection of antituberculosis drugs by liquid chromatography-tandem mass spectrometry

目的:分析使用液相色谱串联质谱法测定肺结核患者血浆中一线抗结核药物血药浓度的情况。方法:采用回顾性研究方法,选取2023年1—12月于山东省公共卫生临床中心因肺结核住院治疗,并进行一线抗结核药物血药浓度测定者作为研究对象,其中,服用乙胺丁醇(EMB;口服,0.75 g,1次/d)者144例,服用异烟肼(INH;口服,0.3 g,1次/d)者209例,服用吡嗪酰胺(PZA;口服,0.75 g,2次/d)者78例,服用利福平(RFP;口服,0.6 g,1次/d)者181例。收集研究对象年龄、性别信息,以及抗结核药物血药浓度测定结果资料,分析研究对象4种一线抗结核药物服药2 h后的血药浓度情况,及其与性别、年龄分布的相关性。结果:服用EMB、INH、PZA、RFP药物2 h后,研究对象血药浓度低于参考浓度范围者分别占62.5%(90/144)、54.1%(113/209)、34.6%(27/78)、22.7%(41/181)。其中,男性患者出现EMB(<2 mg/L)、INH(<3 mg/L)、PZA(<20 mg/L)、RFP(<8 mg/L)低血药浓度者分别占67.4%(64/95)、53.1%(68/128)、38.9%(21/54)、25.9%(30/116);女性患者出现上述药物低血药浓度者分别占53.1%(26/49)、55.6%(45/81)、25.0%(6/24)、16.9%(11/65),差异均无统计学意义(χ^(2)值分别为2.823、0.118、1.416、1.900,P值分别为0.093、0.731、0.234、0.168)。研究对象不同年龄分布与低血药浓度出现比例未见相关。结论:肺结核患者服用一线抗结核药物2 h后,出现低血药浓度的现象普遍存在,出现EMB和INH低血药浓度的比例高于PZA和RFP。

Objective:To assess the plasma concentrations of first-line antituberculosis drugs in patients diagnosed with pulmonary tuberculosis using liquid chromatography-tandem mass spectrometry.Methods:This retrospective study enrolled patients treated for pulmonary tuberculosis at the Shandong Public Health Clinical Center from January to December 2023.Patients included in the analysis underwent first-line antituberculosis drug plasma concentration measurements.The cohort comprised 144 patients administered ethambutol(EMB;0.75 g orally once daily),209 patients given isoniazid(INH;0.3 g orally once daily),78 patients prescribed pyrazinamide(PZA;0.75 g orally twice daily),and 181 patients on rifampicin(RFP;0.6 g orally once daily).Demographic data,including age and gender,as well as the results of blood drug concentration measurements for first-line antituberculosis drugs,were collected.The study analyzed plasma concentrations of EMB,INH,PZA,and RFP two hours post-administration,assessing their correlations with gender and age.Results:Two hours following administration,a significant proportion of patients exhibited plasma drug concentrations below the established reference ranges:62.5%(90/144)for EMB,54.1%(113/209)for INH,34.6%(27/78)for PZA,and 22.7%(41/181)for RFP.Subgroup analyses revealed gender-related differences in plasma drug concentrations below the therapeutic threshold:67.4%(64/95)of male patients for EMB(<2 mg/L),53.1%(68/128)for INH(<3 mg/L),38.9%(21/54)for PZA(<20 mg/L),and 25.9%(30/116)for RFP(<8 mg/L);compared to 53.1%(26/49),55.6%(45/81),25.0%(6/24),and 16.9%(11/65)of female patients for the same drugs,respectively.However,these differences were not statistically significant(χ^(2)values were 2.823,0.118,1.416,and 1.900 with P values of 0.093,0.731,0.234,and 0.168,respectively).Additionally,no correlation was observed between the age distribution of the study subjects and the prevalence of subtherapeutic drug concentrations.Conclusion:It is frequently observed that patients with pulmonary tuberculosis exhibit subtherapeutic plasma concentrations of first-line antituberculosis drugs just two hours post-administration.Notably,the prevalence of low plasma concentrations is higher for EMB and isoniazid INH compared to PZA and RFP.