Objective: To develop a method for simultaneous determination of the plasma drug concentrations of tegacyclin and amikacin in infection in intensive care unit (ICU) patients with carbapenem resistant enterobacteriaceae (CRE) using LC-MS/MS, and apply it to the therapeutic drug monitoring (TDM). Methods: NaOH solution and methanol solution with internal standards of minocycline and kanamycin were added into plasma samples. The resulting solution was then extracted with the mixed solution of ethyl acetate and methylene chloride. The supernatant was dried with nitrogen and re-dissolved in methanol. Determination was carried out with a waters Cortec C18 (100 mm×4.6 mm, 2.7 μm) chromatographic column. Mobile phase A was methanol, mobile phase B was formic acid / ammonium formate aqueous solution, the flow rate was 0.3 mL·min-1, and the injection volume was 2 μL. Electrospray spray ion source, positive ion scanning and multiple reaction monitoring mode were used. Results: The linear range and quantitative limit of tegacyclin and amikacin both met the requirements. The inter-and intra-day precision and matrix effect were all <15%. Samples of ten patients treated with tegacyclin (50 mg, q12h) and amikacin (0.8 g, qd) were collected. The steady-state trough concentrations of tegacyclin and amikacin in ten ICU patients with CRE infection were (83.86±84.56) ng·mL-1 and (83.86±84.56) ng·mL-1, respectively. There were large individual differences caused by the two antibiotics. Conclusion: This method is rapid, sensitive, specific and reproducible. It can be used for clinical TDM of ICU patients with CRE infection.
RAO Zhi, GUO Si-ming, HE Zhong-fang, DANG Zi-long, LI Bo-xia, QIN Hong-yan, WEI Yu-hui
. Simultaneous determination of tegacyclin and amikacin in severe patients plasma with carbapenem resistant enterobacter infection by LC-MS / MS*[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(3)
: 387
-393
.
DOI: 10.16155/j.0254-1793.2023.03.04
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