Amitriptyline hydrochloride is an antidepressant drug with sedative effects used to treat the symptoms of anxiety, agitation with depression and schizophrenia with depression. A reversed‐phase high‐performance liquid chromatography method was developed to separate and quantitatively determine the assay and four organic impurities of amitriptyline in tablet dosage form and bulk drugs using a C18 column in an isocratic elution mode with mobile phase consisting of a mixture of pH 7.5 phosphate buffer and methanol. The pH conditions used in the chromatographic separation are discussed. The stability‐indicating characteristics of the proposed method were proved using stress testing [5 m HCl at 80°C/1 h, 5 m NaOH at 80°C/1 h, H2O (v/w) at 80°C/1 h, 6% H2O2 (v/v) at 25°C/1 h, dry heat at 105°C/24 h and UV–vis light/4 days] and validated for specificity, detection limit, quantitation limit, linearity, precision, accuracy and robustness. For amitriptyline and its four known organic impurities, the quantitation limits, linearity and recoveries were in the ranges 0.25–3.0 μg/ml (r2 > 0.999) and 87.9–107.6%, respectively. The mass (m/z) spectral data of amitriptyline hydrochloride and its impurity are discussed. The proposed LC method is also suitable for impurity profiling and assay determination of amitriptyline in bulk drugs and pharmaceutical formulations.

Montelukast sodium (MLS) is a leukotriene receptor antagonist drug used in the treatment of asthma, bronchospasm, allergic rhinitis and urticaria. A reversed-phase high performance liquid chromatography method was developed to separate, identify and quantitative determination of MLS and its eight known organic impurities in tablet dosage form using a C 18 column and mobile phases consisting of a gradient mixture of pH 2.5 phosphate buffer and acetonitrile. The stability-indicating character of the developed method was proven using stress testing (1 M HCl at 80 C/30 min, 1 M NaOH at 80 C/30 min, H 2 O at 80 C/30 min, 3% H 2 O 2 at 25 C/1 min, dry heat at 105 C/10 h and UV-vis light/4 days) and was validated for specificity, quantitation limit, linearity, precision, accuracy and robustness. For MLS and its eight known impurities, the quantitation limits, linearity and recoveries were 0.015-0.03 μg/ml, correlation coefficient > 0.997 (R 2 > 0.995) and 85.5-107.0%, respectively. The developed chromatographic method is suitable for impurity profiling and also for assay determination of MLS in bulk drugs and pharmaceutical formulations. The mass values (m/z) of newly formed degradation products (DP1 and DP2) of montelukast sodium were identified using liquid chromatography-mass spectrometry.

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An efficient, short and, a convenient asymmetric total synthesis of filamentous fungi related resorcylic acid lactones 7-epi-zeaenol (2) and zeaenol (1) have been achieved in 7 and 9 linear steps with the high overall yield of 32% and 21% respectively, from the known intermediate 13. Mitsunobu inversion, De Brabander’s protocol for macrolactonisation, Heck cross-coupling, diastereoselective alkyne aldehyde coupling and Ohira–Bestmann alkynylation are the key reactions.

Background A simple and reliable HPLC method for the determination of impurities in Eltrombopag olamine (ELO) film-coated tablets were not available. At the same time, there was no official monograph reported. The proposed research targeted at development of a stability-indicating method for determining impurities in ELO film coated tablets and drug substances. Objective To develop and validate a simple and effective HPLC method for the determination of impurities in ELO film-coated tablets and drug substances. Method All the impurities were separated using the RP-HPLC system equipped with Zorbax SB-Phenyl 150 mm x 4.6 mm, 3.5 µm, column with UV detection at 230 nm with the flow rate of 1.2 mL/min. The column temperature was maintained at 45 °C. Results The proposed method was validated as per current regulatory guidelines. The coefficient of correlation was found to be > 0.999 for all impurities. The limit of detection and quantification for ELO and all specified impurities was determined. The precision and accuracy were obtained for ELO and their related impurities. Intra and inter-day % RSD values were between 1.22% to 2.04%, and recovery of impurity varied between 93.80 to 103.69%. The stability of standard and sample solutions was established for 24 hrs. Conclusion As per recent guidelines, a stability-indicating method has been developed to determine the impurities in ELO film-coated tablets and drug substances. QbD-based robustness was performed and proved that the method was robust. Highlights The proposed article is the first-ever RP HPLC method for determining impurities in ELO film-coated tablets and drug substances. QbD concept was utilized to verify the method performance.