Development and validation of UHPLC–MS/MS methods for the quantification of colistin in plasma and dried plasma spots

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 129; pp. 551 - 557
• Main Authors: Cangemi, Giuliana, Barco, Sebastiano, Castagnola, Elio, Tripodi, Gino, Favata, Fabio, D’Avolio, Antonio
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 10.09.2016
• Subjects: Anti-Bacterial Agents - blood; Anti-Bacterial Agents - chemistry; Calibration; Chromatography, High Pressure Liquid - methods; Colistin; Colistin - blood; Colistin - chemistry; Dried Blood Spot Testing - methods; Dried blood spots; Dried plasma spot; Drug Monitoring - methods; Humans; LC–MS; Limit of Detection; Plasma - chemistry; Reproducibility of Results; Tandem Mass Spectrometry - methods; Therapeutic drug monitoring; UHPLC–MS/MS; Therapeutic drug monitoring; UHPLC–MS/MS; Dried plasma spot; Colistin; Dried blood spots; LC–MS
• ISSN: 0731-7085; 1873-264X; 1873-264X
• DOI: 10.1016/j.jpba.2016.08.002

[Display omitted] •A new method to quantify colistin A and B in dried plasma spots (DPS) is reported.•The method was compared to a standard method to quantify colistin in plasma.•Colistin on DPS was found to be stable at least for one week at 20–25°C.•A good correlation was observed among the two chromatographic methods.•DPS is useful to store and ship samples in a cheaper and safer manner. 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 [r2 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.