Determination Of Linezolid In Plasma Research Articles

Nanoparticle-Enhanced Potentiometric Ion-Selective Electrodes for Therapeutic Drug Monitoring of Linezolid

Nosocomial infections caused by multidrug-resistant (MDR) bacteria is treated with Linezolid (LIN) either alone or with other medications such as; Meropenem (MERO) or Theophylline (THEO). LIN has variable pharmacokinetics which makes it an ideal candidate for therapeutic drug monitoring (TDM). Ion selective electrode (ISE) is a promising tool that can be used in hospitals by medical practitioners to adjust the dose of LIN which will eventually improve the therapeutic outcomes. Four potentiometric PVC sensors were fabricated for the determination of LIN in plasma in the presence of co-administered medications (MERO and THEO). Sensor I; cationic exchanger phosphotungstate sensor covering a concentration range of 1.0 × 10−7–1.0 × 10−4 M. while Sensor II; 2–hydroxypropyl-β-cyclodextrin (HP-βCD) sensor covered a concentration range of 1.0 × 10−9–1.0 × 10−3 M. The last two sensors were fabricated using metal nanoparticles (NPs). Sensor III; Copper NP-incorporated HP-βCD sensor was used over a concentration range 1.0 × 10−9–1.0 × 10−3 M, while Sensor IV; Cobalt NP-incorporated HP-βCD sensor attained the highest sensitivity of all the prepared sensors with the quantification range of 1.0 × 10−10–1.0 × 10−4 M. Britton-Robinson buffer at pH 3.5 ± 0.5 was chosen for optimization of experimental conditions of the four sensors. The proposed sensors performance was validated according to IUPAC\\FDA guidelines and was applied successfully for the determination of LIN in its pharmaceutical formulation and for TDM in incurred plasma samples. No interference was noted in the presence of (MERO) and (THEO) that are commonly co-administered with LIN as a part of the treatment protocol for healthcare-associated pneumonia (HCAP).

Voltammetric monitoring of linezolid, meropenem and theophylline in plasma

Treatment of healthcare associated Pneumonia (HCAP) caused by Methicillin-resistant Staphylococcus aureus (MRSA) requires therapeutic protocols formed of linezolid (LIN) either alone or in combination with meropenem (MERO) and theophylline (THEO). The inter-individual pharmacokinetic variations require the development of reliable therapeutic drug monitoring (TDM) tools especially in immunocompromised patients. A sensitive square wave voltammetric sensor using multiwalled carbon nanotubes (MWCNTs) modified carbon paste electrode in Britton-Robinson buffer was developed and validated. Experimental parameters such as pH, percentage of MWCNTs, and pre-concentration time were optimized. The sensor was employed at pH 11.0 for the determination of LIN in plasma within a concentration range of 2.5 × 10−8 - 8.0 × 10−6 mol L−1without interference from co-administered medications. On the other hand, simultaneous monitoring of LIN, MERO and THEO in plasma was feasible at pH 3.0 over concentration ranges of 4.0 × 10−7- 9.0 × 10−5, 8.0 × 10−7- 9.0 × 10−5 and 8.0 × 10−7 - 9.0 × 10−5 mol L−1, respectively. The performance of the proposed sensor was validated and the applicability for TDM has been demonstrated in plasma of healthy volunteers.

Determination of linezolid in plasma and bronchoalveolar lavage by high-performance liquid chromatography with ultraviolet detection using a fully automated extraction method

The aim of this study was to develop a specific and sensitive high-performance liquid chromatographic assay for the determination of linezolid in human plasma, and bronchoalveolar lavage. The sample extraction was based on a fully automated solid-phase extraction with an OASIS HLB cartridge. The method used ultraviolet detection set at a wavelength of 254 nm and a separation with a Zorbax Eclipse XDB C8 column. The assay has been found linear over the concentration range 0.02–30 μg/ml and 0.04–30 μg/ml for linezolid, respectively, in plasma and bronchoalveolar lavage. It provided good validation data for accuracy and precision (CV <4.64% and 5.08%, accuracy in the range 96.93–102.67% and 97.33–105.67%, respectively, for intra- and inter-day). The assay will be applied to determine the penetration of linezolid in human bronchoalveolar lavage during pharmacokinetic steady-state.

Determination of linezolid in plasma by reversed-phase high-performance liquid chromatography

An HPLC–UV method was developed for assay of linezolid in dog, rat, mouse, and rabbit plasma. Linezolid and the internal standard were extracted on a solid phase cartridge (SPE) and separated on a reversed-phase column (C8, 4.6×150 mm, 5 μm) with 20% acetonitrile in water as mobile phase. The SPE quantitatively recovered linezolid and the internal standard from plasma samples. The chromatographic peak height ratio or peak area ratio based on UV absorbency at 251 nm was used for quantitative analysis. The assay procedures were simple and the assay was specific and had adequate precision and accuracy. Calibration standards with concentrations over the range of 0.01–20 μg/ml were validated for routine sample analysis to support the pharmacokinetic and toxicology studies with linezolid in dog, rat, mouse, and rabbit. Analysis of quality control samples showed the coefficients of variation were usually <10% and the measured and theoretical concentrations differed by <10% in most assays. Linezolid in the plasma samples was stable when stored at below −20°C for at least 63 days, at room temperature (22–23°C) for up to 24 h, and after three freeze–thaw cycles. This HPLC method has been successfully used in multiple laboratories to assay plasma samples from pharmacokinetic and toxicology studies with linezolid in the animal species.