Abstract
ABSTRACTA rapid, simple, sensitive and selective LC-MS/MS method has been developed and validated for simultaneous quantification of silodosin and silodosin β-D-glucuronide human plasma using stable labelled isotopes as internal standards. Solid phase extraction technique (SPE) was used for the extraction and the method validated over a range of 0.20 ng/mL to 100.56 ng/mL for silidisin and 0.20 ng/mL to 101.63 ng/mL for silodosin β-D-glucuronide. The chromatographic separation was achieved on Cosmicsil Adze C18 (4.6 × 100 mm, 3 µm) column using a mobile phase consisting of acetonitrile, methanol and 10 mM ammonium acetate buffer 50:20:30 (v/v/v) at a flow rate of 1.000 mL/min with run time of 4 min. The API-4500 LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. The developed assay method was successfully applied to a pharmacokinetic study in humans.
Highlights
An alpha-adrenergic blocker used in the treatment for men with benign prostatic hyperplasia
The monitoring mode (MRM) state file parameters were optimized at a concentration of 50 ng/mL to maximize the response for the analyte
The use of stable labelled isotopes of the analyte as internal standard is recommended for bioanalytical assays to increase assay precision and limit variable recovery between analyte and the IS
Summary
An alpha-adrenergic blocker used in the treatment for men with benign prostatic hyperplasia. It acts as an α1-adrenoceptor antagonist with high uroselectivity. It acts by binding of norepinephrine and epinephrine induces phospholipase C activation, leading to generation of second messengers, including inositol triphosphate and diacylglycerol. These induce an increase in intracellular calcium levels and smooth muscle contraction (Figure 1). Blockage of α1A-AR induces prostatic and urethral smooth muscle relaxation, and may improve voiding symptoms. Silodosin seems to target afferent nerves in the bladder, and thereby acts on bladder over activity and storage symptoms [1,2,3,4,5]
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