Development and validation of a DESI-HRMS/MS method for the fast profiling of esomeprazole and its metabolites in rat plasma: a pharmacokinetic study.
The advances in pharmaceutical development and drug discovery impose the availability of reliable high-throughput screening methods for the rapid evaluation of drug metabolism and pharmacokinetic (PK) in biological samples. Here, a desorption electrospray mass spectrometry (DESI-MS) method has been developed and validated for the PK profiling of esomeprazole and its metabolites (5-hydroxyomeprazole and omeprazole sulfone) in rat plasma. Rats were treated with an esomeprazole solution (2.5 mg/mL) for endovenous administration and the analyte levels were profiled over 2 h after liquid-liquid extraction from plasma. MS and tandem mass spectrometry (MS/MS) experiments were performed by using a DESI-LTQ-Orbitrap XL instrument and an on-spot fixed time analysis on PMMA surfaces. Validation was performed for the esomeprazole. The DESI-MS/MS method exhibited for the esomepazole excellent sensitivity (limit of detection (LOD)=60 ng/mL), linearity (0.2-20 µg/mL concentration range; y=23848(±361)X, n=15; r(2) =0.987) and precision (RSD<9%) by using an internal standard method. The PK results were discussed in terms of Area Under the Curve, Cmax and Tmax . Data reliability was demonstrated by comparison with a liquid chromatography-tandem mass spectrometry method (p>0.05). The data achieved demonstrated that the DESI-MS method is suitable for sensitive and fast profiling of a drug and its metabolites at the therapeutic concentration levels.
Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124, Parma, Italy.
Alessandra
A
Rossi
Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124, Parma, Italy.
Luca
L
Castrati
Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124, Parma, Italy.
Paolo
P
Colombo
Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124, Parma, Italy.
Lisa
L
Flammini
Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124, Parma, Italy.
Elisabetta
E
Barocelli
Ruggero
R
Bettini
Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/A, 43124, Parma, Italy.
Lisa
L
Elviri
D000818:Animals; D019540:Area Under Curve; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D064098:Esomeprazole / Q000097:blood* / Q000493:pharmacokinetics*; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives; D054328:Proton Pump Inhibitors / Q000097:blood* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D054328:Proton Pump Inhibitors; C040450:omeprazole sulfone; D009853:Omeprazole; D064098:Esomeprazole
DESI-HRMS; esomeprazole; pharmacokinetic