First report on clorprenaline HCl degradation products: identification and characterization by LC-MS/MS

Clorprenaline hydrochloride (CLOR), beta(2) adrenergic agonist, was used for the therapeutic treatment for bronchial asthma. It is important to know the stability behavior of the drug in various degradation conditions because the drug is incompatible with strong oxidizing agent and strong base. The main objective of the study was to identify and characterize degradation products of clorprenaline HCl by LC-MS/MS. The mass-compatible method was developed, validated and further used for LC-MS/MS. In reverse-phase high-performance liquid chromatography (RP-HPLC), the resolution was achieved using Phenomenex C-18 (250 x 4.6 mm, 5 mu) column and ammonium acetate buffer (5 mM), 0.1% TEA, pH 6.5 with acetic acid/methanol (70:30, v/v) as mobile phase. The flow rate was 1 mL/min. The wavelength was selected for UV detection at 215 nm. Different forced degradation conditions such as hydrolytic (acidic and basic), oxidative, thermal and sunlight have been applied according to ICH Q1A (R2) guidelines to derive stability of the drug. Further, the method was validated as per ICH Q2 (R1) guidelines. The degradation product was characterized by LC-MS/MS using ESI in positive ion mode. Potential degradation product DP (36.87% of total degradation) was found in basic condition, while no degradation was observed in acidic, neutral, sunlight, oxidation and thermal conditions. The stability indicating analytical method was found to be novel, simple, specific, selective, sensitive, accurate, precise and robust for the determination of clorprenaline HCl.