DEVELOPMENT AND VALIDATION OF HPLC-DAD METHOD FOR THE DETERMINATION OF BISOPROLOL IN TABLET DOSAGE FORMS

Objective: A rapid, simple and sensitive RP-HPLC method was developed and validated for the determination of bisoprolol fumarate in bulk and pharmaceutical dosage form. Methods: Chromatographic separation was achieved within 2.5 min on ACQUITY Arc System, Waters Symmetry C18 column (3.9 mm i.d. X 150 mm, 5 μm particle sizes) using a mobile phase consisted of acetonitrile: phosphate buffer (25:75 v/v) in an isocratic mode at a flow rate of 1.4 ml/min. The pH of the mobile phase was adjusted to 7.0 with orthophosphoric acid and UV detection was set at 226 nm. Results: The retention time for bisoprolol fumarate was found to be 2.09 min. The proposed method was validated according to ICH guidelines with respect to linearity, specificity precision, accuracy and robustness. The limit of detection and limit of quantification are calculated and found to be 0.4825 and 1.4621 μg/ml; respectively. Conclusion: The proposed method can help research studies, quality control and routine analysis with lesser resources available. The results of the assay of pharmaceutical formulation of the developed method are highly reliable and reproducible and is in good agreement with the label claim of the medicines

DEVELOPMENT AND VALIDATION OF HPLC METHOD FOR THE SIMULTANEOUS DETERMINATION OF ENALAPRIL MALEATE IN PRESENT OF THEIR IMPURITIES: APPLICATION TO TABLET ANALYSIS

Objective: A simple, rapid, economical, and highly sensitive stability-indicating HPLC method was developed and fully validated for determination of enalapril maleate in presence of its related substances namely enalaprilat dihydrate and diketopiperazine.Methods: Chromatographic separation was achieved on Grace Platinumр C8 EPS column (4.6 mm i.d. X 250 mm, 5 μm) at room temperature. The mobile phase consisted of acetonitrile: 20 mmol phosphate buffer adjusted to pH 2.2 (25:75 v/v) isocratically pumped at a flow rate 2 ml/min and UV-detection was monitored at 215 nm.Results: The proposed method was validated according to ICH guidelines with total run time less than 9 min. The correlation coefficient (r2) was noted as 0.99981 which states that the method was good linear to the concentration versus peak area responses. The developed method found to be high sensitivity with LOD and LOQ of 0.021 and 0.062 %; respectively. The developed, validated method was successfully applied for the determination of enalapril maleate in presence of their impurities in tablet dosage form.Conclusion: A rapid, economical, simple and sensitive HPLC method was developed and validated for the determination of enalapril maleate in tablet dosage form in presence of their impurities. The developed method can help research studies, quality control and routine analysis with lesser resources available. Therefore, the proposed validated method is fast and reliable and can be used for routine quantitative analysis as well as quality control of enalapril maleate in pharmaceutical formulation

Development of Methods of Quality Control of the Tablets «Ramipril»

Our main target was to develop methods for the quality control of the tablet «ramipril» according to the indicators of «Quantitative determination», «Impurities» and «Dissolution». New, precise, accurate and green HPLC methods were developed for the determination of ramipril and its impurities in tablets. The separation was accomplished using a diode array detector at 210 nm with an isocratic and gradient mobile phase consisting of a 0.2 g/L solution of sodium hexanesulfonate (pH 2.7) and the acetonitrile and chromatographic columns Acclaim 120 C18 and Inertsil ODS-3. The developed method was validated in accordance with ICH guidelines. The analysis of impurities was performed within a run duration of less than 25 min, which is about a two times shorter than that of the official Ph. Eur. method. The analysis of ramipril in tablets was performed with a run duration of less than 4.5 min, which is about three times shorter than that of the official USP method. The developed methods were successfully applied for the quality control of the tablet «ramipril» according to the indicators of «Quantitative determination», «Impurities» and «Dissolution». In addition, they proved its superiority over the reported methods in terms of greenness using different assessment tools

DEVELOPMENT OF HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR THE SIMULTANEOUS ANALYSIS OF AMLODIPINE AND VALSARTAN IN COMBINED DOSAGE FORM AND IN VITRO DISSOLUTION STUDIED

 Objective: A simple, rapid, and reproducible high-performance liquid chromatography method was developed for the simultaneous determination of amlodipine and valsartan in their combined dosage forms and for drug dissolution studies.Methods: A C18 column (Zorbax Eclipse ХDB-C18, 5 μm, 2.1 mm × 150 mm) and a mobile phase of water:acetonitrile:trifluoroacetic acid (55:45:0.1 v/v/v) mixture were used for separation and quantification. Analyses were run at a flow rate of 0.4 mL/min and at ambient temperature. The injection volume was 5 μL and the ultraviolet detector was set at 265 nm. The method was validated as per ICH guidelines.Results: Under these conditions, amlodipine and valsartan were eluted at 1.64 min and 4.08 min, respectively. Total run time was shorter than 7 min. The results were 99.6 ± 0.6 and 98.5 ± 0.8 for amlodipine and valsartan, respectively. Valsartan was released within 15 min (98.32%) and amlodipine was also released within 30 min (96.16%) both at a pH of 6.8.Conclusion: The developed method was applied successfully for quality control assay of amlodipine and valsartan in their combination drug product and in vitro dissolution studies

Ультра ефективна рідинна хроматографія – мас-спектрометричні методики визначення залишкових кількостей раміприлу та гідрохлоротіазиду для контролю очистки обладнання

Monitoring the completeness of equipment cleaning is essential to prevent cross-contamination of medicinal products. Therefore, it is necessary to develop fast and sensitive methods for studying residual quantities of active ingredients on the surfaces of technological equipment. The aim of the work was to develop and validate analytical methods for the determination of ramipril and hydrochlorothiazide in wash waters by ultra-performance liquid chromatography–mass spectrometry method. Materials and methods. In the study, standard samples of ramipril (USP RS) and hydrochlorothiazide (USP RS), as well as class A reagents, were used. Samples were analysed on a liquid chromatograph with an MS detector (Agilent 6420 and Waters Xevo TQD ACQUITY). We used the Kinetex C18 column (2.1 mm × 30 mm × 1.7 μm); mobile phase – 0.1% formic acid solution in deionised water – Acetonitrile (ratio 73:27 for the determination of ramipril and 91.5:8.5 for the determination of hydrochlorothiazide); mobile phase rate of 0.4 mL/min for the determination of ramipril and 0.35 mL/min for the determination of hydrochlorothiazide; column temperature 45 °C for the determination of ramipril and 40 °C for the determination of hydrochlorothiazide, ionisation mode - electric spray in positive mode; The detection parameters are the mode of registration of the daughter ion 417 → 234 m/z for the determination of ramipril and 298 → 281 m/z for the determination of hydrochlorothiazide. Results and discussion. Methods for the determination of ramipril and hydrochlorothiazide in wash waters by ultra-performance liquid chromatography–mass spectrometry have been developed. The developed methods have sufficient linearity, correctness and precision. The sensitivity of the techniques was confirmed at the level of 0.0026 μg/ml. The techniques can be used in the concentration range of 0.0026 – 0.0255 μg/ml Conclusions. Analytical methods for determining ramipril and hydrochlorothiazide in wash waters have been developed and validated.Контроль повноти очищення обладнання є важливим для запобігання перехресної контамінації лікарських засобів. Тому необхідно розробити швидкі й чутливі методики дослідження залишкових кількостей активних інгредієнтів на поверхнях технологічного обладнання. Мета роботи – розробити і валідувати аналітичні методики визначення раміприлу та гідрохлортіазиду у промивних водах методом ультра-ефективної рідинної хроматографії з МС- детектуванням. Матеріали та методи. При проведенні дослідження використовували стандартні зразки раміприлу (USP RS) та гідрохлортіазиду (USP RS), а також реактиви класу А. Зразки аналізували на рідинному хроматографі з МС- детектором (Agilent 6420 та Waters Xevo TQD ACQUITY). Використовували колонку Kinetex С18 (2.1 мм × 30 мм × 1.7 мкм); рухома фаза – 0.1 % розчин мурашиної кислоти в деіонізованій воді - Ацетонітрил (співвідношення 73:27 для визначення раміприлу та 91.5:8.5 для визначення гідрохлортіазиду); швидкість рухомої фази 0.4 мл/хв для визначення раміприлу та 0.35 мл/хв для визначення гідрохлортіазиду; температура колонки 45 °С для визначення раміприлу та 40 °С для визначення гідрохлортіазиду, режим іонізації - електроспрей у позитивному режимі; параметри детектування - режим реєстрації дочірнього іону 417 → 234 m/z для визначення раміприлу та 298 → 281 m/z для визначення гідрохлортіазиду. Результати та обговорення. Розроблено методики визначення раміприлу та гідрохлортіазиду у промивних водах методом ультра-ефективної рідинної хроматографії з МС- детектуванням. Розроблені методики має достатню лінійність, правильність і прецизійність. Чутливість методик підтверджено на рівні 0.0026 мкг/мл. Методики можна застосовувати в діапазоні концентрацій 0.0026 – 0.0255 мкг/мл. Висновки. Розроблено та валідовано аналітичні методики визначення раміприлу та гідрохлортіазиду у промивних вода

DEVELOPMENT OF ULTRA-HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR THE DETERMINATION OF CAPTOPRIL IN PHARMACEUTICAL DOSAGE FORMS

Objective: The objective of this research was to develop more simple, sensitive, accurate, and less expensive analytical methods for the determination of captopril in medicines by Ultra-high-performance liquid chromatography.Materials and Methods: The chromatographic analysis of captopril performed on liquid chromatography Agilent 1290 Infinity II LC System.Results: A simple, rapid, sensitive, and specific method was developed for the determination of captopril by ultra-high-performance liquid chromatography in mono-medicines and pharmaceutical dosage forms in combination with hydrochlorothiazide without previous separation. Satisfactory resolution was achieved using Fused-Core® technology Ascentis Express C18 column (4.6×150 mm) and a mobile phase consisting of methanol and 0.1% solution of trifluoroacetic acid (40/60, v/v) at a flow rate 1.2 mL/minute and the wavelength detection was 220 nm. Ascentis Express columns, based on Fusеd-core pаrticle technоlogy, prоvide more than twice the speed and efficiency of traditiоnal cоlumns at half the backpressure of sub-2-μm columns. The retention time for captopril was 1.345 minute. The validation of this method was based on the ICH and USP guidelines.Conclusion: The results obtained in this research work clearly indicated that the assay was rapid, sensitive and successfully applied to the determination of both drugs in pharmaceutical dosage forms without interference from tablet excipients

DEVELOPMENT OF ULTRA-HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR THE DETERMINATION OF CAPTOPRIL IN PHARMACEUTICAL DOSAGE FORMS

Objective: The objective of this research was to develop more simple, sensitive, accurate, and less expensive analytical methods for the determination of captopril in medicines by Ultra-high-performance liquid chromatography.Materials and Methods: The chromatographic analysis of captopril performed on liquid chromatography Agilent 1290 Infinity II LC System.Results: A simple, rapid, sensitive, and specific method was developed for the determination of captopril by ultra-high-performance liquid chromatography in mono-medicines and pharmaceutical dosage forms in combination with hydrochlorothiazide without previous separation. Satisfactory resolution was achieved using Fused-Core® technology Ascentis Express C18 column (4.6×150 mm) and a mobile phase consisting of methanol and 0.1% solution of trifluoroacetic acid (40/60, v/v) at a flow rate 1.2 mL/minute and the wavelength detection was 220 nm. Ascentis Express columns, based on Fusеd-core pаrticle technоlogy, prоvide more than twice the speed and efficiency of traditiоnal cоlumns at half the backpressure of sub-2-μm columns. The retention time for captopril was 1.345 minute. The validation of this method was based on the ICH and USP guidelines.Conclusion: The results obtained in this research work clearly indicated that the assay was rapid, sensitive and successfully applied to the determination of both drugs in pharmaceutical dosage forms without interference from tablet excipients