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A Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneously Determining Meropenem and Linezolid in Blood and Cerebrospinal Fluid

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초록

Antibiotic therapy requires appropriate dosage of drugs for effective treatment. Too low an- tibiotic concentrations may lead to treatment failure and the development of resistant pathogens, whereas overdosing may cause neurological side effects or hemolytic dis- eases. Meropenem and linezolid are used only in the treatment of serious infections or when other antibiotics are no longer effective as well as for treating central nervous sys- tem infections. It is difficult or sometimes even impossible to predict the relation between dosing of antibiotics and its cerebrospinal fluid (CSF) concentration; thus, a method of de- termining antibiotics not only in the blood but also in the CSF is needed. Analytical method validation is an integral part of good laboratory practice and ensures high accuracy of the results. We performed complete validation process according to the Food and Drug Admin- istration and European Medicine Agency, covering the aspects precision, specificity, accu- racy, recovery, limit of detection, limit of quantification, stability, carry-over, and matrix ef- fects. Our liquid chromatography-tandem mass spectrometry method for the simultaneous measurement of meropenem and linezolid in different matrix meets all the acceptance criteria. The method was successfully applied to determine meropenem and linezolid con- centrations in serum and CSF samples obtained from children treated with these antibiot- ics.

Abstract

Antibiotic therapy requires appropriate dosage of drugs for effective treatment. Too low an- tibiotic concentrations may lead to treatment failure and the development of resistant pathogens, whereas overdosing may cause neurological side effects or hemolytic dis- eases. Meropenem and linezolid are used only in the treatment of serious infections or when other antibiotics are no longer effective as well as for treating central nervous sys- tem infections. It is difficult or sometimes even impossible to predict the relation between dosing of antibiotics and its cerebrospinal fluid (CSF) concentration; thus, a method of de- termining antibiotics not only in the blood but also in the CSF is needed. Analytical method validation is an integral part of good laboratory practice and ensures high accuracy of the results. We performed complete validation process according to the Food and Drug Admin- istration and European Medicine Agency, covering the aspects precision, specificity, accu- racy, recovery, limit of detection, limit of quantification, stability, carry-over, and matrix ef- fects. Our liquid chromatography-tandem mass spectrometry method for the simultaneous measurement of meropenem and linezolid in different matrix meets all the acceptance criteria. The method was successfully applied to determine meropenem and linezolid con- centrations in serum and CSF samples obtained from children treated with these antibiot- ics.

참고문헌 (20)

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