Novel LC–MS/MS Method for the Quantification of Silodosin and its Metabolites in Human Plasma

Abstract

Benign prostatic hyperplasia (BPH) is a medical condition caused by the enlargement of the prostate gland as a result of hyperplasia of both the glandular epithelial and stromal cell compartments [1]. BPH has become a major cause for the increasing number of lower urinary tract symptoms (LUTS) in men, such as frequent urination, a weak urine stream and dribbling of urine, which can all worsen a patient's quality of life. This disease generally appears at the age of 50 or above in males and is comorbid with hypertension and erectile dysfunction. Moreover, the demographics of the population across the world indicate that aging is one of the most prominent causes of such health issues. To study the symptoms associated with BPH and bladder outlet obstruction, it is essential to have innovative strategies that can withstand the test of changing times. In response to this need, several safe and effective medical treatment options have been introduced to alleviate the symptoms at an early stage to lower the disease progression rate.Over the last two decades, α-adrenoceptor (α-AR) antagonists have become the first-line treatment therapy for men with LUTS, suggestive of bladder outlet obstruction caused by BPH. Initially, phenoxybenzamine, a nonselective first generation α 1 -and α 2 -AR antagonist was used to treat LUTS. However, it received limited success because of its associated orthostatic and dizziness-related side effects on account of its poor tolerability. In October 2008, the US FDA approved silodosin as the second, third-generation α 1A selective antagonist after tamsulosin for the management of BPH. It has demonstrated significant effectiveness in improving the storage/irritating and voiding/obstructive symptoms compared with a placebo [2]. Furthermore, in a urodynamic study, silodosin assisted in improving detrusor overactivity and in reducing the grade of obstruction [3]. Silodosin is highly selective for the α 1A -AR, with an affinity that is 583-and 55.5-fold higher than that for the α 1B -and α 1D -ARs, respectively [3,4]. Compared to the currently available α 1 -AR antagonists, silodosin is 1400-times more specific in terms of α 1A -AR versus α 1B -AR binding than doxazosin and terazosin and 40-times greater compared with tamsulosin. Such increased selectivity for α 1A -AR is envisaged to provide additional relief from LUTS in patients with BPH without increasing the rate of serious adverse cardiovascular events [5]. In this editorial, we evaluate the capabilities and scope of the existing bioanalytical methods and propose a novel fit-for-purpose liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method in human plasma that can meet the current requirements for the analysis of silodosin and its metabolites.Bioanalytical platforms for silodosin: past, present & future Since its approval in 2008, there have been very few bioanalytical methods developed for the quantitation of silodosin [6][7][8]. LC-MS/MS so far has been the preferred technique for analysis; however, a complete account of bioanaly...

Development and validation of an epithelial–mesenchymal transition-related gene signature for predicting prognosis

“…A previous study indicated that 6-thioguanosine, which inhibits PTHrP transcription, was used in the treatment of leukemia[ 34 ]. Phenoxybenzamine, a nonselective first-generation α1- and α2-AR antagonist, has been administered to treat lower urinary tract symptoms[ 35 ]. Medrysone is a corticosteroid usually administered to cure eye inflammation[ 36 ].…”