Simple and high sample throughput LC/ESI-MS/MS method for bioequivalence study of prazosin, a drug with risk of orthostatic hypotension. (2nd September 2022)

• Record Type: Journal Article
• Authors: Loh, Gabriel Onn Kit; Wong, Emily Yii Ling; Tan, Yvonne Tze Fung; Wee, Hong Chin; Ng, Ru Shing; Syed, Haroon Khalid; Peh, Kok Khiang
• Is Part Of: Drug development and industrial pharmacy. Volume 48:Number 9(2022)
• Page Start: 470
• Page End: 479
• Publication Date: 2022-09-02
• Subjects: Prazosin -- orthostatic hypotension -- bedside sampling -- protein precipitation -- sensitive -- human plasma -- bioequivalence; Pharmaceutical chemistry -- Periodicals; Pharmaceutical industry -- Periodicals; Drug Industry -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615.05
• DOI: 10.1080/03639045.2022.2125985
• Languages: English
• ISSNs: 0363-9045

Abstract

Abstract: Objective: The study aimed to develop a rapid, simple and sensitive LC/ESI-MS/MS method to measure prazosin concentration in human plasma and apply bedside sampling in bioequivalence study of two prazosin tablets to resolve the adverse effect of orthostatic hypotension. Significance: The LC/ESI-MS/MS prazosin method was highly sensitive and selective. Bedside sampling reduced the orthostatic hypotension incidence and subject dropout rate. Methods: After sample preparation, prazosin and terazosin (IS) were detected on mass spectrometer operating in multiple reaction monitoring mode using positive ionization. Mobile phase flow rate was set at 0.40 mL/min with sample run time of 1.75 min. The bioanalytical method was validated as per EMEA and FDA guidelines. Bedside sampling was performed in bioequivalence study for the first 4 h after dosing. The three primary pharmacokinetic parameters, C max, AUC0- t and AUC0-∞ and 90% confidence interval were determined. Results: The small injection volume of 1 μL minimized instrumentation contamination and prolonged the analytical column lifespan. Linearity was obtained between 0.5 and 30.0 ng/mL, with coefficient of determination, r 2 ≥ 0.99. The mean extraction recovery of prazosin and IS was >92%, with precision value (CV, %) ≤ 10.3%. Only two orthostatic hypotension adverse events were reported. The two prazosin formulations were found to be bioequivalent. Conclusion: The LC/ESI-MS/MS method has shown robustness and reliability exemplified by the incurred sample re-analysis result. Bedside sampling should be proposed for bioequivalence or pharmacokinetic studies of drugs demonstrating adverse event of orthostatic hypotension.