Establishment of clinical sampling process for therapeutic drug monitoring of linezolid based upon whole blood stability studies
OBJECTIVE To establish a high performance liquid chromatography(HPLC)method for measuring linezolid in human plasma and create a clinical sampling process based upon a whole blood stability study to enhance the comprehensive investi-gation of whole blood stability and advance the clinical sampling procedure,offering references for precise linezolid therapeutic drug monitoring(TDM)and personalized drug dosing scheme formulation,as well as fostering the standardization and uniformity of anti-infective drug TDM system.METHODS Plasma samples were treated with an internal standard(cefoperazone)and pre-cipitated with a solution of acetonitrile(0.1％formic acid).The supernatant was diluted with water(1∶1,V/V)and subsequently loaded.Separation of the components was achieved on a Shim-pack GIST C18 column(4.6 mm×250 mm,5.0 μm)with a mobile phase consisting of 50 mmol·L-1 potassium dihydrogen phosphate containing 0.05％formic acid-acetonitrile(75∶25,V/V).Flow rate was set at 1.0 mL·min-1.Detection was performed at a wavelength of 254 nm and a column temperature of 40 ℃.The study examined the stability of linezolid in whole blood and plasma samples under varying temperatures and sampling vessels.Based upon the findings from the analysis of whole blood stability,the development of clinical sampling and testing protocols and the clinical implementation of TDM were implemented.RESULTS The concentration range of linezolid exhibited a strong linear relationship within a range of 0.59-23.40 μg·mL-1(r2＞0.999).The lower limit of quantization was 0.59 μg·mL-1.The extraction recoveries for low,medium and high concentrations were 95.97％-111.35％.Additionally,intraday and daytime pre-cision RSD values were＜8.72％.The linezolid in whole blood samples in heparin sodium collection tubes remained stable within 24 h at room temperature(18-23 ℃)and in a 4 ℃ refrigerator.It was superior to EDTA-K2 collection tubes under the same con-ditions(stable within 12 h).Additionally,plasma quality control samples underwent pretreatment and stabilization in an automatic injector at 6℃ for 24 h.Plasma samples remained stable when stored at 4 ℃,room temperature(18-23 ℃)for 24 h,frozen at-80 ℃ for 65 days and subjected to freeze-thaw cycles at-80 ℃ for 3 times.CONCLUSION The utilization of the established linezolid TDM method and clinical sampling process can effectively maintain the stability of linezolid and enhance the precision of test outcomes.Furthermore,these practices may offer valuable references for the standardization and harmonization of linezolid TDM procedures.
linezolidtherapeutic drug monitoringwhole blood stabilityclinical sampling processHPLC
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