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.

Apalutamide, an androgen receptor inhibitor, is used to treat prostate cancer. A stability-indicating high-performance liquid chromatography method was developed for the estimation of assay and organic impurities of apalutamide in drug substance and in tablet dosages using Design of Experiments. The chromatographic separation was achieved within 30 min using Atlantis dC 18 , 100 Â 4.6 mm, 3.0 μm and the binary gradient program (10 mM KH 2 PO 4 , pH 3.5; acetonitrile). The detection wavelength, flow rate, column temperature and injection volume used were 270 nm, 1.0 ml/min, 45 C and 10 μl, respectively. The interaction of independent variables (pH, column temperature and flow rate) and their influences on HPLC parameters were studied using a central composite design, and then the peak separation and elution behaviors between apalutamide and its seven impurities were determined. The method validation was performed for linearity, detection limit, quantitation limit, accuracy, precision and robustness as per the International Conference on Harmonization. A high-quality recovery with good precision (91.7-106.0%) and correlations (r 2 > 0.997) within a linear range of 0.12-2.24 μg/ml (0.05-0.3%, w/w) were achieved consistently for assay and organic impurities of apalutamide. The stabilityindicating characteristics of the proposed method were assessed through forced degradation and mass balance studies. An effort was made to figure out the chemical structures of newly formed degradation products (DP1-DP5) using LC-MS/MS.

Lacosamide (LA) is an antiepileptic medicine that is used to treat tonic–clonic seizures, partial‐onset seizures, mental problems, and pain. A simple, effective, and reliable normal‐phase liquid chromatographic technique was developed and validated to separate and estimate the enantiomer of (S‐enantiomer) LA in pharmaceutical drug substance and drug product. Normal‐phase LC was performed using USP L40 packing material (250 × 4.6 mm, 5 μm) and a mobile phase of n‐hexane and ethanol at 1.0 ml min−1. The detection wavelength, column temperature, and injection volume used were 210 nm, 25°C, and 20 μl, respectively. The enantiomers (LA and S‐enantiomer) were completely separated using a minimum resolution of 5.8 and accurately quantified without any interference in a 25‐min run time. Accuracy study for stereoselective and enantiomeric purity trials was conducted between 10 and 200%, with recovery values ranging from 99.4 to 103.1% and linear regression values >0.997. The stability‐indicating characteristics were assessed using forced degradation tests. The proposed normal‐phase HPLC technique is an alternate approach to the official monograph methods (USP and Ph.Eur.) of LA, and it was successfully used in the evaluation of release and stability samples for both tablet dosage forms and pharmaceutical substances.