A Sensitive Liquid Chromatography-Mass Spectrometric Method for Determination of Bisoprolol in Rat Serum after Pre-Column Derivatization

• Published in: Journal of chromatographic science 2024-08, Vol.62 (7), p.668-675
• Main Authors: Shaheen, Huda A, Bahaffi, Saleh O, Khedr, Alaa M
• Format: Article
• Language: English
• Subjects: Animals; Bisoprolol - blood; Bisoprolol - chemistry; Bisoprolol - pharmacokinetics; Chromatography, Liquid - methods; Limit of Detection; Linear Models; Male; Mass Spectrometry - methods; Rats; Rats, Sprague-Dawley; Reproducibility of Results
• ISSN: 0021-9665; 1945-239X; 1945-239X
• DOI: 10.1093/chromsci/bmad056

Abstract Two derivatization regents were reacted with bisoprolol (BIS), followed by liquid-chromatography-mass spectrometric analysis. 3-Bromomethyl-propyphenazone (BMP) and dansyl-chloride (Dns-Cl) were reacted via the secondary amino group using a catalyst to accelerate the reaction progress and completeness with minimal reaction byproducts. The sensitivity and the ionization efficiency of both BIS-methyl-propyphenazone (BIS-MP) and BIS-Dns via electrospray ionization were studied. The sensitivity of BIS-MP was superior to BIS-Dns. The derivatization procedure, extraction procedure, and LC-MS method were optimized and validated to achieve the monitoring of BIS in rat serum at a picogram scale. The calibration curve showed a regression coefficient value of 0.999 within a concentration spanning a range of 10–500 pg/mL. The detection limit and quantitation were 4 and 10 pg/mL, respectively. The intraday and inter-day precision values (% relative standard deviation) ranged from 0.53 to 6.91%, whereas the accuracy values (expressed as % error) ranged from −4.20 to −0.77%. The pharmacokinetic parameters were: 15,280 pg/mL for a maximum concentration of BIS (Cmax) at the maximum time (Tmax) of 1 h. BIS’s elimination half-life (t1/2) was determined to be 3 h. The value of the area under the concentration-time curve (AUC0 − t) was 34,370 pg/mL h.