title: Development and validation of a new UPLC-PDA method to quantify linezolid in plasma and in dried plasma spots.
abstract: Linezolid is an oxazolidinone antibiotic used for the treatment of pneumonia and uncomplicated and complicated skin and soft tissues infections caused by Gram positive bacteria. It is also used as second line agent in multi-drug resistant tuberculosis. Therapeutic drug monitoring (TDM) of linezolid represents a valid tool in clinical practice to optimize therapy, especially in critically ill patients. Spreading of TDM is mainly limited by high costs shipment and lack of laboratories that offer a TDM service. To overcome these problems, the use of dried plasma spots or dried blood spots is increasing. The aim of this work was to develop and validate a new chromatographic method to analyze linezolid in plasma and in dried plasma spots and to evaluate the correlation between the two extraction methods. Linezolid extraction from plasma and from dried plasma spots was obtained using acetonitrile. Quinoxaline was used as internal standard. Analysis was performed by an ultra performance liquid chromatography (UPLC) system coupled with photo diode array (PDA) detector, at 254nm. Both analytical methods were linear (r(2)>0.999) over the calibration range of 30-0.117mg/L. Limit of quantification and limit of detection were 0.117mg/L and 0.058mg/L, respectively. Intra and inter-day precision (R.S.D.%) and accuracy (%) were <15%. Long term stability of linezolid in dried plasma spots showed absence of degradation at room temperature (20-25°C) and at 4°C, for at least one month. Linear regression analysis confirmed that the two methods of extraction have good correlation. Thus they are suited for TDM of linezolid and for pharmacokinetic studies.
authors: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Corso Svizzera 164, 10149, Turin, Italy. Electronic address: lorena.baietto@unito.it.
authors: Lorena
authors: L
authors: Baietto
authors: Antonio
authors: A
authors: D'Avolio
authors: Alessandra
authors: A
authors: Ariaudo
authors: Silvia
authors: S
authors: Corcione
authors: Marco
authors: M
authors: Simiele
authors: Jessica
authors: J
authors: Cusato
authors: Rosario
authors: R
authors: Urbino
authors: Giovanni
authors: G
authors: Di Perri
authors: V Marco
authors: VM
authors: Ranieri
authors: Francesco Giuseppe
authors: FG
authors: De Rosa
mesh_terms: D000081:Acetamides / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D059788:Dried Blood Spot Testing / Q000379:methods*; D016903:Drug Monitoring; D004355:Drug Stability; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D000069349:Linezolid; D023303:Oxazolidinones / Q000097:blood*; D015203:Reproducibility of Results
chemical_list: D000081:Acetamides; D023303:Oxazolidinones; D000069349:Linezolid
keywords: Dried plasma spots; HPLC; Human plasma; Linezolid; Stability; Therapeutic drug monitoring TDM; UPLC