关键词: 串联质谱法, 结核,肺, 抗结核药, 药物监测

Abstract:

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 (χ² 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.

Key words: Tandem mass spectrometry, Tuberculosis, pulmonary, Antitubercular agents, Drug monitoring