Simultaneous Determination of Linezolid and Levamisole Hydrochloride in a Fixed Dose Combination

Kumar, Lalit; Yadav, Yugvijay Singh; Rathnanand, Mahalaxmi

doi:10.5530/ijper.51.4.91

Cited by 2 publications

(2 citation statements)

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“…Another advantage of the present method over previously reported methods is the application of fully automatic injection techniques and the relatively short detection time, meeting the need for rapid and accurate detection. [7][8][9][10][11]18,19 As seen in Figure 3, the closeness of experimental data from the in vitro PK/PD infection model and the simulated pharmacokinetic curve up to 24 h suggests the reliability of the model in simulating drug concentrations over time and the concentration remained above 2mg/L during the 3 days treatment. As shown in Table 4, there are minor differences between the experimental parameters and simulated parameters analyzed by Phoenix Winnonlin 8.3, demonstrating the successful establishment of the in vitro PK/PD model.…”

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Development and Validation of an HPLC-UV Method for Quantitation of Linezolid: Application to Resistance Study Using in vitro PK/PD Model

Guang¹,

Yan²,

Mao³

et al. 2021

IDR

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Background: Linezolid (LNZ), an oxazolidinone antibiotic, has 100% oral bioavailability and favorable activities against gram-positive pathogens. The in vitro PK/PD model was developed based on concentrations obtained with routine doses in humans can be used to guide dose optimization in the clinic. Methods: In this study, we employed an in vitro PK/PD model to simulate the changes in the plasma concentration of linezolid in the human body against a clinical isolate of MRSA in vitro. A high-performance liquid chromatography (HPLC)-UV method was applied to measure the concentration of linezolid. Bacterial samples were collected at different times from the central compartment for count. Results: The chromatographic separation was carried out with an AichromBond-AQC18 column (250mm×4.6mm, 5μm), using a mobile phase of water with 0.1% formic acid:acetonitrile 70:30 (v/v), followed by detection at 254 nm, and a single detection run was completed within 10 min. The method was validated by estimating the precision and accuracy for the inter-and intra-day analyses in the concentration range of 0.25-32 mg/L. The method was linear over the investigated range of 0.125-32 mg/L, with all correlation coefficients R 2 = 0.9999. The intra-day and inter-day precisions were within 7.598%, and the method recovery ranged from 90.912% to 106.459%. In vitro PK/PD model, both the absorption and elimination of linezolid being simulated can be precisely controlled by computer. In the control group, the bacterial reached 7.9 Log10CFU/mL in the first 48h and maintained until the end, indicating that the colonies grew well in vitro PK/PD model. In the linezolid 600 mg q12h administration group, the colony decreased to 2.39 Log10CFU/mL at 24h, showing a good bactericidal effect; however, the colonies resumed growth to the initial level in 48h, indicating an emergence of resistance. Conclusion:We successfully established an in vitro infection PK/PD model and developed an HPLC-UV method to determine linezolid concentration for resistance investigation. The results suggest that the 600 mg q12h dosing regimen may no longer be applicable and requires optimization.

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confidence: 75%