Search

A simple and robust high‐performance liquid chromatography (HPLC) method was developed for organic impurities of hydroxyzine hydrochloride in pharmaceuticals. The developed method was designed to estimate all organic impurities of hydroxyzine. The HPLC separation was achieved using C18 column (150 × 3.9 mm, 5 μm) along with a binary gradient consisting of mobile phases A (0.1%, trifluoroacetic acid in purified water) and B (0.05%, trifluoroacetic acid in acetonitrile), a flow rate of 0.7–mL/min, a column temperature of 30°C and a sample temperature of 25°C. The detection wavelength used was 230 nm for the estimation of impurity‐A, impurity‐B, and all unspecified impurities and degradation products, whereas impurity‐C was quantitated using 254 nm. The stability‐indicating property of the developed HPLC technique was assessed using stress testing conditions of hydrolysis, oxidation, thermal, photo‐light, and humidity. The validation study was performed for the limit of detection and limit of quantification, linearity, and recoveries were 0.03%, 0.05%, and 0.1132–2.9920 μg/mL (R2 > 0.999), and 84.09%–109.74%, respectively. The proposed method is highly suitable for the determination of assay, organic impurities, and degradation products of the hydroxyzine. The chemical structure of degradation product 1 (hydroxyzine N‐Oxide) and degradation product 2 (O‐Acetyl hydroxyzine) were identified with the supporting data of LC‐mass spectrometry (LC‐MS) and high‐resolution MS. [ABSTRACT FROM AUTHOR]

The R,S‐enantiomer impurity and diastereomer impurities (S,S‐isomer and R,R‐isomer) of the solifenacin (S,R‐enantiomer) were effectively separated and quantified simultaneously utilizing normal‐phase high‐performance liquid chromatography with a chiral stationary phase consisting of amylose tris (3,5‐dimethylphenylcarbamate) coated on silica‐gel (Chiralpak, AD‐H). The enantiomeric and stereo‐selective separation was achieved within a run time of 35 minutes using a mobile phase of 'n‐hexane, ethanol, and diethylamine' in an isocratic elution mode with a detection wavelength of 220 nm. The validation attributes assessed were accuracy (which showed excellent recoveries between 97.5% and 100.4%) and linearity (which was proven in the range of 0.081–1.275 μg.mL−1, with a linear regression of 0.999). The stress testing experiments proved that the developed methodology by the HPLC technique has stability‐indicating characteristics, as all closely eluting peak pairs were separated well with a resolution of 2.3 and without any interference. The proposed methodology was highly efficient in separating and simultaneously determining the chiral impurities (enantiomers and diastereomers) of the solifenacin in the release and stability sample analyses of drug substances and tablets in pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Propranolol hydrochloride (PPH) is a medication of beta‐adrenergic receptors. It is used to treat pediatric hemangiomas that are growing and need systemic therapy. A reversed‐phase high‐performance liquid chromatography (HPLC) was made to separate and estimate the amounts of ten known organic impurities of propranolol in bulk drugs, tablets, and capsule dosage forms. The chromatographic separation was achieved on a C18 column (100 × 4.6 mm, 2.7 μm) using a binary gradient mixture of pH 2.3 phosphate buffer and organic modifiers of acetonitrile, methanol, and isopropyl alcohol as the mobile phase. The stability‐indicating character of the proposed method was proven using stress testing study. The test method was validated for specificity, limit of detection, limit of quantitation, linearity, precision, accuracy, and robustness. For the propranolol and its ten organic impurities, the limit of quantitation, linearity, and recoveries were found in a range of 0.0123–0.4266 μg/mL (R2 > 0.9982) and 89.2–98.9%, respectively. The proposed liquid chromatography method is found to be highly suitable for impurity profiling of propranolol in bulk drugs and pharmaceutical formulations (tablets and capsules). [ABSTRACT FROM AUTHOR]

The present research developed and validated a new stability‐indicating technique for the stereo‐selectively enantiomers of the antiviral nucleoside analog Valacyclovir hydrochloride (VAL). The chiral separation was performed using normal‐phase high‐performance liquid chromatography (HPLC) with a chiral stationary phase consisting of amylose tris(3‐chloro‐5‐methylphenylcarbamate) and a mobile phase of "n‐hexane, methanol, ethanol, and diethylamine", flow rate of 0.60 mL/min, column temperature of 30°C, injection volume of 10‐μL, detection wavelength of 254‐nm, and run time of 25‐min. The enantiomers (S‐enantiomer, L‐isomer, R‐enantiomer, and D‐isomer) of Valacyclovir were separated with a resolution of 4.8 and no interference. The validation parameters verified for the proposed method, linearity in a range of 0.1002–24.3486 μg/mL (0.02–4.86%) with a regression coefficient of 0.999, and the accuracy was determined with excellent recoveries ranging from 94.38%–109.97%. The concentrations established for the detection limit and quantitation limit were 0.01% and 0.02%, respectively. The forced degradation experiments were used to assess the stability‐indicating qualities. D‐Valacyclovir impurity was successfully evaluated in release and stability samples of VAL in drug substance and tablet dosage forms using the proposed normal phase chiral HPLC approach. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 dC18, 100 × 4.6 mm, 3.0 μm and the binary gradient program (10 mm KH2PO4, 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 (r2 > 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 stability‐indicating 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. [ABSTRACT FROM AUTHOR]