Rapid simultaneous determination of indacaterol maleate and glycopyrronium bromide in inhaler capsules using a validated stability-indicating monolithic LC method

Abstract

BackgroundChronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. A combination of indacaterol maleate with glycopyrronium bromide has recently been approved as a once-daily maintenance therapy in patients with COPD. The very low dose (μg level/capsule) renders the analysis of such products challenges. This study reports for the first time about HPLC method for the quality control of such combination and it is a stability indicating at the same time.ResultsA rapid, simple, precise and reproducible HPLC method was developed and validated for simultaneous determination of indacaterol maleate and glycopyrronium bromide using tenoxicam as an internal standard. The chromatographic separation was achieved on an onyx monolithic C18 column (100 × 4.6 mm) using a mobile phase consisting of acetonitrile and 30 mM phosphate buffer (pH 3.5) (30:70, v/v), run at a flow rate of 2 mL/min with UV detection at 210 nm. The total analysis time was less than 3 min. The HPLC method was validated for linearity, limits of detection and quantitation, precision, accuracy, system suitability and robustness. Calibration curves were obtained in the concentration ranges of 1–44 µg/mL for indacaterol maleate and 0.5–20 µg/mL for glycopyrronium bromide. Stability tests were done through exposure of the analyte solution for different stress conditions and the results indicate no interference of degradants with HPLC method.ConclusionsThe method was successfully applied for the quantitative analysis of indacaterol maleate and glycopyrronium bromide both individually and in a combined pharmaceutical inhaler capsules to support the quality control and to assure the therapeutic efficacy of the two drugs. The simple procedure involved in sample preparation and the short run-time added the important property of high throughput to the method. Graphical abstractChemical structures and representative HPLC chromatogram of indacaterol maleate (IND; 22 μg/mL), glycopyrronium bromide (GLY; 10 μg/mL) and tenoxicam (IS, 15μg/mL) in commercial capsules.

Identification and characterization of degradation products of indacaterol using liquid chromatography/mass spectrometry

“…1,3 Indacaterol maleate (IND), 5-[2-[(5,6-Diethyl-2, 3-dihydro-1H-inden-2-yl)amino]-1-hydroxyethyl]-8hydroxyquinolin-2(1H)-one, is a long acting b 2agonist (LABA) that stimulates b 2 -receptors, with increased intracellular cyclic adenosine monophosphate (cAMP) levels. 4 This results in improvement of muscle smoothness surrounding the bronchial tubes. It is a once-daily treatment with approved dose long acting b-adrenoceptor agonist (LABA) that improves health status in people with breathlessness, and exacerbation of patients with COPD.…”

“…[9][10][11][12][13][14] Preceding published reports reveal few spectrophotometric 15,16 and HPLC methods for IND. 4,17 However, none of the above studies reported the characterization of DPs of IND. Hence, the current study focuses on the characterization of IND and its stress degradants by using UPLC/DAD/ESI-QTOF and MS/MS method.…”

Voltammetric determination of glycopyrrolate in a pharmaceutical formulation

“…10 Zayed and Belal used the HPLC method for determination of a combination of indacaterol maleate and glycopyrronium bromide using tenoxicam as an internal standard. 11 Hussein et al used a potentiometric method for glycopyrrolate determination; they fabricated and studied three different kinds of ion-selective potentiometric sensors using multiwalled carbon nanotubes, polyaniline nanoparticles, and polyaniline microparticles. 12 The aim of this work is the determination of glycopyrrolate in pharmaceutical preparations using different voltammetric techniques, namely linear sweep voltammetry (LSV), cyclic voltammetry (CV), and differential pulse voltammetry (DPV).…”