Vol.:(0123456789) 1 3 Journal of the Iranian Chemical Society https://doi.org/10.1007/s13738-019-01831-y ORIGINAL PAPER First report on clorprenaline HCl degradation products: identifcation and characterization by LC–MS/MS Krunal J. Prajapati 1  · Charmy S. Kothari 1 Received: 2 May 2019 / Accepted: 16 December 2019 © Iranian Chemical Society 2019 Abstract Clorprenaline hydrochloride (CLOR), β 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 × 4.6 mm, 5 µ) column and ammonium acetate bufer (5 mM), 0.1% TEA, pH 6.5 with acetic acid/ methanol (70:30, v/v) as mobile phase. The fow rate was 1 mL/min. The wavelength was selected for UV detection at 215 nm. Diferent 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, specifc, selective, sensitive, accurate, precise and robust for the determination of clorprenaline HCl. Keywords Clorprenaline HCl · Identifcation · Characterization · Stability indicating analytical method · LC–MS/MS Abbreviations TEA Trimethylamine UV Ultraviolet spectroscopy ICH International Council for Harmoni- sation of Technical Requirements for Pharmaceuticals for Human Use DP Degradation product HPLC High-performance liquid chromatography % RSD % Relative standard deviation HCl Hydrochloric acid NaOH Sodium hydroxide H 2 O 2 Hydrogen peroxide AR Analytical reagent PVDF Polyvinylidene difuoride PDA Photodiode array detector RBF Round-bottom fask NTP Number of theoretical plates LOD Limit of detection LOQ Limit of quantitation RT Room temperature ESI-ion trap MS/MS Electrospray ionization-ion trap mass spectrometry TIC Total ion chromatogram List of symbols mm Millimeter μ Micron mM Millimolar mL/min Milliliter per minute nm Nanometer μL Microliter µg/mL Microgram per milliliter r Correlation coefcient λ Wavelength °C Celsius t R Retention time * Charmy S. Kothari charmy.kothari@nirmauni.ac.in; charmyshah@gmail.com 1 Department of Pharmaceutical Analysis, Institute of Pharmacy, Nirma University, Sarkhej-Gandhinagar Highway, Post: Chandlodia, Via: Gota, Ahmedabad, Gujarat 382 481, India