Alosetron-d3 Hydrochloride

Alosetron is s Serotonin 5HT3-receptor antagonist that is used in treatment of irritable bowel syndrome.

Alosetron, a 5-HT3 receptor antagonist, delays colonic transit in patients with irritable bowel syndrome and healthy volunteers.[Pubmed:10848662]

Aliment Pharmacol Ther. 2000 Jun;14(6):775-82.

BACKGROUND: Alosetron is a potent and selective 5-HT3 receptor antagonist, which has been shown to be beneficial in the treatment of female patients with non-constipated irritable bowel syndrome. AIMS: To investigate the effect of alosetron on whole gut, small bowel and colonic transit in patients with irritable bowel syndrome (Study 1) and healthy volunteers (Study 2). SUBJECTS: Thirteen patients with irritable bowel syndrome and 12 healthy volunteers. METHODS: Both studies were randomized, double-blind, placebo-controlled with a two-way crossover design, in which each subject received alosetron (2 mg b.d. administered orally) or placebo for 8 days. Mean whole gut transit was determined from the excretion of radio-opaque markers; small bowel transit was determined from rise in breath hydrogen after a meal; and colonic transit and segmental transit were evaluated from abdominal X-ray. In addition, colonic transit was calculated by subtracting small bowel transit time from whole gut transit time. RESULTS: Alosetron increased colonic transit time by prolonging left colonic transit in both patients with irritable bowel syndrome and controls. This resulted in a tendency for the whole gut transit to be delayed in irritable bowel syndrome patients (P=0.128), which was confirmed in controls (P=0.047). CONCLUSION: Alosetron delays colonic transit by prolonging left colonic transit. These results add to the body of evidence suggesting that alosetron should have a therapeutic role in patients with non-constipated irritable bowel syndrome.

Application of a UPLC-MS/MS method for the analysis of alosetron in human plasma to support a bioequivalence study in healthy males and females.[Pubmed:25761551]

Biomed Chromatogr. 2015 Oct;29(10):1527-34.

A simple, rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed and validated for the determination of alosetron (ALO) in human plasma. The assay method involved solid-phase extraction of ALO and ALO 13C-d3 as internal standard (IS) on a LichroSep DVB-HL (30 mg, 1 cm(3) ) cartridge. The chromatography was performed on an Acquity UPLC BEH C18 (50 x 2.1 mm, 1.7 microm) column using acetonitrile and 2.0 mm ammonium formate, pH 3.0 adjusted with 0.1% formic acid (80:20, v/v) as the mobile phase in an isocratic mode. For quantitative analysis, the multiple reaction monitoring transitions studied were m/z 295.1/201.0 for ALO and m/z 299.1/205.1 for IS in the positive ionization mode. The method was validated over a concentration range of 0.01-10.0 ng/mL for ALO. Post-column infusion experiment showed no positive or negative peaks in the elution range of the analyte and IS after injection of extracted blank plasma. The extent of ion-suppression/enhancement, expressed as IS-normalized matrix factor, varied from 0.96 to 1.04. The assay recovery was within 97-103% for ALO and IS. The method was successfully applied to support a bioequivalence study of 1.0 mg alosetron tablets in 28 healthy Indian male and female subjects.

Development of a Forced Degradation Profile of Alosetron by Single Mode Reversed-Phase HPLC, LC-MS, and its Validation.[Pubmed:26839817]

Sci Pharm. 2014 Dec 29;83(2):311-20.

Determination of alosetron in the presence of its degradation products was studied and validated by a novel HPLC method. The separation of the drug and its degradation products was achieved with the Jones Chromatography C18 analytical column (150 mm x 4.6 mm; 3 microm) with a stationary phase in isocratic elution mode. The mobile phase used was 0.01 M ammonium acetate, pH-adjusted to 3.5 with glacial acetic acid and acetonitrile in the ratio of 75:25 (V/V) at a flow rate of 1 ml/min and UV detection was carried out at 217 nm. Further, the drug was subjected to stress studies for acidic, basic, neutral, oxidative, and thermal degradations as per ICH guidelines and the drug was found to be labile in base hydrolysis and oxidation, while stable in acid, neutral, thermal, and photolytic degradation conditions. An MS study has been performed on the major degradation products to predict the degradation pathway of alosetron. The method provided linear responses over the concentration range of 100-1500 ng/ml and regression analysis showed a correlation coefficient value (r(2)) of 0.994. The LOD and LOQ were found to be 1 ng/ml and 3 ng/ml, respectively. The developed LC method was validated as per ICH guidelines with respect to accuracy, selectivity, precision, linearity, and robustness.