Simple and fast LC-MS/MS method for quantification of terazosin in human plasma and application to bioequivalence study
Introduction
Terazosin is an α1-adrenoceptor antagonist is used to treat the symptoms of hypertension and benign prostatic hyperplasia (BPH) [1], [2], [3], [4]. It is a selective, quinazoline-derived post-synaptic alpha-1 antagonist [5], [6]. Its hypotensive action is due to the relaxation of peripheral blood vessels by the competitive antagonism of post-synaptic alpha-adrenoceptors. [7].
Several terazosin analytical methods in human plasma [8], [9], [10], [11], [12], [13], [14], [15], [16], rabbit plasma [17] and pharmaceutical products [14], [16], [18] have been published. The limitations with the use of high performance liquid chromatography (HPLC) methods were insufficient sensitivity, utilization of large plasma sample volume, huge injection volume or long test run time [11], [12], [13]. The disadvantages of liquid-liquid extraction (LLE) methods [8], [11], [12], [15], [19] used for quantification of terazosin in biological samples were labour-intensive, utilization of large volumes of organic solvents and the recycling of used organic solvents is costly while the limitations with the use of solid phase extraction (SPE) methods [13] were time consuming, cumbersome and the SPE cartridges are expensive. These methods may not be suitable for the analysis of large number of samples. The fluorescence spectrofluorimetry using protein precipitation technique [16], [18], [20], [21] was not chromatography method and not feasible to be used in pharmacokinetic and bioequivalence study. Zavitsanos and Alebic-Kolbah [10] reported LC-MS method with LLOQ of 0.0625 ng/mL but using liquid-liquid extraction and injection volume of 20 μL. Therefore, there is a need to develop a fast, simple, high throughput and specific method for determination of terazosin in human plasma for pharmacokinetic and bioequivalence study using simple protein precipitation method.
In the current study, we aim to develop a fast, simple, sensitive and high throughput ultra-fast HPLC tandem mass spectrometry (UHPLC-MS/MS) method for the quantification of terazosin in human plasma using simple protein precipitation method. The effect of different anticoagulants on sensitivity of terazosin was studied. The method was validated in accordance with international guidelines and utilized in a bioequivalence study of 2 mg terazosin in Malaysian healthy volunteers.
Section snippets
Materials
Terazosin hydrochloride (92.1% purity) and prazosin hydrochloride (99.9% purity, internal standard, IS) were purchased from Vivan Life Sciences Pvt. Limited (Thane, India). Formic acid (HPLC grade, >98% purity), acetonitrile (HPLC grade) and methanol (HPLC grade) were purchased from Merck (Darmstadt, Germany). Citrate phosphate dextrose (CPD) blank plasma was obtained from Hospital Pulau Pinang (Pulau Pinang, Malaysia) while dipotassium ethylenediaminetetraacetic acid (K2EDTA) blank plasma was
Method development
During method development, terazosin and prazosin exhibited a stronger ESI response in positive ionization mode with optimized MRM conditions. Acidic mobile phase (0.1% formic acid) was utilized in the study as proton donor. Q1 and Q3 scans were performed to obtain the precursor ions [M + H]+ of terazosin and IS which were 388.20 and 384.20, respectively. MRM was performed to select two product ions for terazosin and IS, at m/z 290.10 and m/z 95.05 for quantification, while m/z 71.15 and m/z
Conclusion
In conclusion, the developed and validated UHPLC-MS/MS method was simple, fast, sensitive and high-throughput for determination of terazosin in human plasma. The method was successfully applied to a bioequivalence study of two terazosin formulations. The simple protein precipitation method showed sufficient sample clean-up with negligible matrix effects. ISR results assured the reproducibility of the method.
CRediT authorship contribution statement
Gabriel Onn Kit Loh: Conceptualization, Methodology, Supervision, Writing - original draft. Emily Yii Ling Wong: Methodology, Validation, Investigation. Yvonne Tze Fung Tan: Formal analysis, Software. Loke Meng Ong: Investigation, Formal analysis, Data curation, Supervision. Ru Shing Ng: Data curation, Project administration. Hong Chin Wee: Investigation, Data curation, Project administration. Kok Khiang Peh: Visualization, Supervision, Writing - review & editing.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
The research was sponsored by Y.S.P. Industries (M) Sdn. Bhd. The test and reference products of the study were provided by Y.S.P. Industries (M) Sdn. Bhd.
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