A simple HPLC-MS/MS method for the determination of polymyxin B in human plasma and its application in the pharmacokinetic study in elderly patients infected with multidrug-resistant Gram-negative bacteria.
Front Pharmacol
; 15: 1396307, 2024.
Article
em En
| MEDLINE
| ID: mdl-39221151
ABSTRACT
Introduction:
Polymyxin B is widely used to treat infections caused by multidrug-resistant Gram-negative bacteria. However, the pharmacokinetic study data of PB in the elderly are scarce. Herein, a simple method to measure the concentration of PB in human plasma was developed and validated by high performance liquid chromatography-tandem mass spectrometry, and it was applied to a PK study in the elderly.Methods:
PB was extracted from human plasma by a rapid protein-precipitation method using 0.1% formic acid in methanol and then separated on an ultimate AQ-C18 column using linear gradient elution with a 0.5-mL/min flow rate. Subsequently, PB was detected using a mass spectrometer operated in positive-ion and multiple-reaction-monitoring modes.Results:
The lower limits of quantification of the method for Polymyxin B1 and Polymyxin B2 were 1.00 and 0.10 µg/mL, respectively. The linear ranges for PB1 and PB2 were 1.00-20.02 and 0.10-2.04 µg/mL, respectively. Patients receiving a 75-mg maintenance dose every 12h had AUCss, 24 h, and Css, av values of 117.70 ± 37.03 µg h/mL and 4.14 ± 1.74 µg/mL, respectively. For patients receiving a 100 mg maintenance dose, these values were 152.73 ± 70.09 µg h/mL and 5.43 ± 2.85 µg/mL, respectively.Conclusion:
The validated HPLC-MS/MS method was successfully applied to a study on the pharmacokinetics of PB in elderly patients infected with multidrug-resistant Gram-negative bacteria. Both two dose strategies in this study would have a excessive PB exposure in the elderly patients then the therapeutic window recommended by guidelines.
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MEDLINE
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En
Ano de publicação:
2024
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Article