Quantitative Determination of Polymyxin E in Human Plasma by LC-MS/MS and Its Clinical Application

OBJECTIVE To establish a simple, low-cost and rapid high performance liquid chromatography tandem mass spectrometry(LC-MS/MS) method for the detection of polymyxin E concentration in plasma.

METHODS Zinc sulfate solution and acetonitrile were used as precipitating agent, polymyxin B1 was used as internal standard. A Thermo Accucore aQ(50 mm×2.1 mm, 2.6 μm) column was used for separation. The mobile phase consisted of methanol-water containing 0.1% formic acid. Gradient elution mode was used, and the column temperature was set at 50 °C. The mass spectrometry was performed in the electrospray positive ion mode, and the multi-reaction monitoring mode was used for quantitative determination. The ion transitions of polymyxin E1, polymyxin E2, polymyxin B1 as internal standard were m/z 585.512→535.256, m/z 578.462→528.489 and m/z 602.675→100.971.

RESULTS A method based on LC-MS/MS was developed for the determination of polymyxin E. The linear relationship between concentration of polymyxin E1 and polymyxin E2 was found to be well within the ranges of 0.058–17.407 µg·mL⁻¹ and 0.100–30.000 µg·mL⁻¹, respectively. The intra day and inter day precision and the verification of matrix effects were both met the established criteria.

CONCLUSION The pre-treatment procedure of this method is simple and economical, and has been validated. It is also suitable for monitoring the plasma concentration of polymyxin E and pharmacokinetic studies in patients with polymyxin E mesylate and polymyxin E sulfate.