title: Development and validation of UHPLC-MS/MS methods for the quantification of colistin in plasma and dried plasma spots.
abstract: Quantification of colistin in plasma samples may be very useful in optimizing therapy especially in special patients' population. Nevertheless, therapeutic drug monitoring of colistin is still limited probably for the low number of laboratories which perform this analysis and for high shipment costs. We developed and validated new UHPLC-MS/MS methods to quantify colistin in plasma and in dried plasma spots (DPS) collected on dried sample spots devices (DSSD). Colistin A, Colistin B and polimixin B, used as internal standard, were detected using multiple reaction monitoring (MRM) of the following specific transitions: 585.5→534.9; 576, 578.5→527.9; 568.9 and 602.5→100.9, 551.9, 592.8, respectively. Colistin A and B were extracted from plasma using protein precipitation and from DSSD using an extraction basic solution. Both methods were validated, and the mean intra and inter-day accuracies and precisions were in accordance with FDA and EMA guidelines. Colistin in DPS was found to be stable for at least one week at room temperature (20-25°C). A statistically significant linear correlation was found between colistin extracted from plasma and from DPS [r(2) 0.9864 (P<0.0001, 95% CI 0.9699-0.9939) for colistin A and 0.9695 (P<0.0001, 95% CI 0.9310-0.9866) for colistin B, respectively]. DPS on DSSD represents a safe and cheap strategy to store and ship at room temperature plasma samples. Thus, it is suited for pharmacokinetic studies and therapeutic drug monitoring of colistin.
authors: Clinical Pathology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors: Giuliana
authors: G
authors: Cangemi
authors: Clinical Pathology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors: Sebastiano
authors: S
authors: Barco
authors: Infectious Disease Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors: Elio
authors: E
authors: Castagnola
authors: Clinical Pathology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors: Gino
authors: G
authors: Tripodi
authors: Department of Medical Sciences, University of Turin, Laboratory of Clinical Pharmacology and Pharmacogenetics, Amedeo di Savoia Hospital, Turin, Italy.
authors: Fabio
authors: F
authors: Favata
authors: Department of Medical Sciences, University of Turin, Laboratory of Clinical Pharmacology and Pharmacogenetics, Amedeo di Savoia Hospital, Turin, Italy. Electronic address: antonio.davolio@unito.it.
authors: Antonio
authors: A
authors: D'Avolio
mesh_terms: D000900:Anti-Bacterial Agents / Q000097:blood / Q000737:chemistry; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003091:Colistin / Q000097:blood* / Q000737:chemistry*; D059788:Dried Blood Spot Testing / Q000379:methods; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D057230:Limit of Detection; D010949:Plasma / Q000737:chemistry*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin
keywords: Colistin; Dried blood spots; Dried plasma spot; LC–MS; Therapeutic drug monitoring; UHPLC–MS/MS