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Fast and sensitive HPLC/UV method for cefazolin quantification in plasma and subcutaneous tissue microdialysate of humans and rodents applied to pharmacokinetic studies in obese individuals.

Fast and sensitive HPLC/UV method for cefazolin quantification in plasma and subcutaneous tissue microdialysate of humans and rodents applied to pharmacokinetic studies in obese individuals.
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Palma EC, Laureano JV, de Araújo BV, Meinhardt NG, Stein AT, Costa TD,


Palma EC, Laureano JV, de Araújo BV, Meinhardt NG, Stein AT, Costa TD, (click to view)

Palma EC, Laureano JV, de Araújo BV, Meinhardt NG, Stein AT, Costa TD,

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Biomedical chromatography : BMC 2018 04 14() e4254 doi 10.1002/bmc.4254
Abstract

Antimicrobial prophylactic dosing of morbidly obese patients may differ from normal weighted individuals due to alterations on drug´s tissue distribution. Drug subcutaneous tissue distribution can be investigated by microdialysis patients and animals. The need of cefazolin prophylactic dose adjustment in obese patients remains under discussion. The paper describes the validation of an HPLC-UV method for cefazolin quantification in plasma and microdialysate samples from clinical and pre-clinical studies. A C18 column with an isocratic mobile phase was used for drug separation, with detection at 272 nm. Total and unbound cefazolin LLOQ was 5 μg/mL in human plasma, 2 μg/mL in rat plasma, 0.5 μg/mL and 0.025 μg/mL in human and rat microdialysate samples, respectively. The maximum intra and inter-day imprecision were 10.7% and 8.1%, respectively. The inaccuracy was lower than 9.7%. Both LOQ imprecision and inaccuracy were below 15%. Cefazolin stability in the experimental conditions was confirmed. Cefazolin plasma concentrations and subcutaneous tissue penetration were accessed by microdialysis in morbidly obese patients (2 g i.v. bolus) and diet-induced obese rats (30 mg/kg i.v. bolus) using the method. This method has the main advantages of easy plasma clean-up and practicability and has proven to be useful in cefazolin clinical and pre-clinical pharmacokinetic investigations.

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