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To establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determining the plasma concentration of the active component polymyxin E in patients treated with colistimethate sodium.
Polymyxin B1 was used as an internal standard, and solid phase extraction (SPE) was employed to process the samples. The chromatographic column was a Kinetex C18 (3 mm×100 mm, 2.6 μm). Mobile phase A was an aqueous solution containing 0.1% formic acid and 5 mmol·L-1 ammonium acetate, and mobile phase B was a methanol solution containing 0.1% formic acid. Gradient elution was performed at a flow rate of 0.5 mL·min-1. An electrospray ionization (ESI) source was used with positive ion multiple reaction monitoring (MRM) for detection. The ion pairs for quantitative analysis were as follows: m/z 585.6→241.1 (polymyxin E1), m/z 578.6→227.2 (polymyxin E2), and m/z 602.6→101.2 (polymyxin B1). The selectivity, standard curve, residues, precision and accuracy, extraction recovery rate, matrix effect and stability of the method were investigated, and the plasma concentrations of polymyxin E1 and E2 in patients treated with colistimethate sodium were measured.
The linear relationships of polymyxin E1 and E2 concentrations were good within the ranges of 0.02–3.86 μg·mL-1 and 0.03–5.65 μg·mL-1, respectively. The lower limits of quantification (LLOQ) for polymyxin E1 and E2 were 0.02 μg·mL-1 and 0.03 μg·mL-1, respectively. The standard curve equations for polymyxin E1 and E2 are Y=4.55×10-1X-2.92×10-2 (r=0.994 2)、Y=8.61×10-1X-1.38×10-2 (r=0.996 4), respectively. The within-day and day-to-day precision, accuracy, extraction recovery, matrix effects, and stability of polymyxin E1 and E2 all met the methodological requirements. Using this method, the AUC of polymyxin E in 26 patients receiving colistimethate sodium ranged from 28.42 to 317.51 μg·mL-1.
This method is accurate, sensitive, rapid, and stable, and can be used for the determination of the plasma concentrations of polymyxin E1 and E2 in human plasma.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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