Polypill is a fixed-dose combination that contains three or more active ingredients used as a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects.A novel and a...Polypill is a fixed-dose combination that contains three or more active ingredients used as a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects.A novel and accurate liquid chromatography tandem mass spectrometry method using electrospray ionization mode has been developed and validated for the simultaneous determination of amlodipine（AMD）,valsartan（VAL） using losartan（LOS） as an internal standard（IS）,and hydrochlorothiazide（HCT） using furosemide（FSD） as an IS.The separation was carried on Aquasil C18（50 mm×2.1 mm,5μm） reversed phase column using acetonitrile and water containing 0.1%formic acid（50：50,v/v） as the mobile phase.The method was validated in terms of linearity,accuracy and precision over the concentration range of 1-1000 ng/mL.The intra and inter-day precision and accuracy,stability and extraction recoveries of all the analytes were in the acceptable range.This method can be successfully applied to the pharmacokinetic study of AMD,VAL and HCT when given as a polypill.展开更多
A sensitive and selective method has been proposed for the simultaneous determination of amlodipine(AML),valsartan(VAL) and hydrochlorothiazide(HCTZ) in human plasma by liquid chromatography–tandem mass spectrometry...A sensitive and selective method has been proposed for the simultaneous determination of amlodipine(AML),valsartan(VAL) and hydrochlorothiazide(HCTZ) in human plasma by liquid chromatography–tandem mass spectrometry(LC–MS/MS). The analytes and their deuterated analogs were quantitatively extracted from100 μL human plasma by solid phase extraction on Oasis HLB cartridges. The chromatographic separation of the analytes was achieved on a Chromolith RP18 e(100 mm × 4.6 mm) analytical column within 2.5 min. The resolution factor between AML and VAL, AML and HCTZ, and VAL and HCTZ was 2.9, 1.5 and 1.4, respectively,under isocratic conditions. The method was validated over a dynamic concentration range of 0.02–20.0 ng/m L for AML, 5.00–10,000 ng/m L for VAL and 0.20–200 ng/m L for HCTZ. Ion-suppression/enhancement effects were investigated by post-column infusion technique. The mean IS-normalized matrix factors for AML, VAL and HCTZ were 0.992, 0.994 and 0.998, respectively. The intra-batch and inter-batch precision(% CV) across quality control levels was ≤ 5.56% and the recovery was in the range of 93.4%–99.6% for all the analytes. The method was successfully applied to a bioequivalence study of 5 mg AML + 160 mg VAL + 12.5 mg HCTZ tablet formulation(test and reference) in 18 healthy Indian males under fasting. The mean log-transformed ratios of C max, AUC0–120 h and AUC0-inf and their 90% CIs were within 90.2%–102.1%. The assay reproducibility was demonstrated by reanalysis of 90 incurred samples.展开更多
Amlodipine/valsartan(Aml/Val)single-pill combination(SPC)therapy has been widely used and studied in clinical practice in recent years.This article reviews the Chinese and English literature on the clinical use of Aml...Amlodipine/valsartan(Aml/Val)single-pill combination(SPC)therapy has been widely used and studied in clinical practice in recent years.This article reviews the Chinese and English literature on the clinical use of Aml/Val SPC therapy in Chinese hypertensive patients.According to five studies concerning the efficacy and safety of this treatment,Aml/Val SPC therapy was more efficacious than monotherapy with valsartan,amlodipine,or the nifedipine gastrointestinal therapeutic system.This treatment showed greater blood pressure-lowering effects,a higher blood pressure control rate,and a higher response rate.Aml/Val SPC treatment was well tolerated,with adverse event rates similar to those of monotherapy with valsartan or amlodipine and significantly rarer adverse events compared with the nifedipine gastrointestinal therapeutic system.Aml/Val SPC is a highly efficacious and well-tolerated antihypertensive treatment in Chinese hypertensive patients.展开更多
A simple, sensitive, and specific method was developed for simultaneous determination of Amlodipine besylate (AML), Valsartan (Vals) and Hydrochlorothiazide (HCT) by high performance liquid chromatography without prev...A simple, sensitive, and specific method was developed for simultaneous determination of Amlodipine besylate (AML), Valsartan (Vals) and Hydrochlorothiazide (HCT) by high performance liquid chromatography without previous separation. Satisfactory resolution was achieved using a RP-C18 chromatographic column, Phenomenex Kinetex (150 mm × 4.6 mm i.d) and a mobile phase consisting of acetonitrile-phosphate buffer (0.05 M) with pH 2.8 in the proportion of (40/60, v/v) at a flow rate 0.8 mL/min and the wavelength detection was 227 nm. The retention time for HCT, AML and VAls was 2.26, 3.16 and 11.19 min;respectively. The described method was linear over a range of 4-28 μg /ml, 5-40 μg /ml and 1-12 μg /ml for AML, Vals and HCT;respectively. The mean percent recoveries were 99.94%, 99.96% and 99.78% for AML, Vals and HCT;respectively. F-test and t-test at 95%con?dence level were used to check the intermediate precision data obtained under different experimental setups. The method could be used for analysis of combined dose tablet formulation containing AML, Vals, HCT as well as spiked human plasma.展开更多
New HPLC method was developed for determination of amlodipine and valsartan in their binary mixture as a part of routine control of combined formulations. The method was validated to meet official requirements includi...New HPLC method was developed for determination of amlodipine and valsartan in their binary mixture as a part of routine control of combined formulations. The method was validated to meet official requirements including selectivity, stability, linearity, precision and accuracy. Chromatography was carried out using a LiChrospher RP-18 column, a mixture containing acetonitrile, phosphate buffer of pH 3.5 and methanol (45:45:10, v/v/v) and new fluorescence detection at 255 nm for excitation and 448 nm for emission. The effect of methanol content, pH of the buffer, flow rate, detection wavelengths and column temperature was estimated in robustness study, according to a plan defined by the Plackett-Burman design. For identification of significant effects, both graphical and statistical methods were used. Ro-bustness for dissolution test was checked estimating the effects of paddle speed, temperature and pH of dissolution medium. The method was proved to complying with all official guidelines. Therefore, it is suitable for determination of amlodipine and valsartan in their binary mixtures for different analytical and pharmaceutical purposes.展开更多
文摘Polypill is a fixed-dose combination that contains three or more active ingredients used as a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects.A novel and accurate liquid chromatography tandem mass spectrometry method using electrospray ionization mode has been developed and validated for the simultaneous determination of amlodipine（AMD）,valsartan（VAL） using losartan（LOS） as an internal standard（IS）,and hydrochlorothiazide（HCT） using furosemide（FSD） as an IS.The separation was carried on Aquasil C18（50 mm×2.1 mm,5μm） reversed phase column using acetonitrile and water containing 0.1%formic acid（50：50,v/v） as the mobile phase.The method was validated in terms of linearity,accuracy and precision over the concentration range of 1-1000 ng/mL.The intra and inter-day precision and accuracy,stability and extraction recoveries of all the analytes were in the acceptable range.This method can be successfully applied to the pharmacokinetic study of AMD,VAL and HCT when given as a polypill.
文摘A sensitive and selective method has been proposed for the simultaneous determination of amlodipine(AML),valsartan(VAL) and hydrochlorothiazide(HCTZ) in human plasma by liquid chromatography–tandem mass spectrometry(LC–MS/MS). The analytes and their deuterated analogs were quantitatively extracted from100 μL human plasma by solid phase extraction on Oasis HLB cartridges. The chromatographic separation of the analytes was achieved on a Chromolith RP18 e(100 mm × 4.6 mm) analytical column within 2.5 min. The resolution factor between AML and VAL, AML and HCTZ, and VAL and HCTZ was 2.9, 1.5 and 1.4, respectively,under isocratic conditions. The method was validated over a dynamic concentration range of 0.02–20.0 ng/m L for AML, 5.00–10,000 ng/m L for VAL and 0.20–200 ng/m L for HCTZ. Ion-suppression/enhancement effects were investigated by post-column infusion technique. The mean IS-normalized matrix factors for AML, VAL and HCTZ were 0.992, 0.994 and 0.998, respectively. The intra-batch and inter-batch precision(% CV) across quality control levels was ≤ 5.56% and the recovery was in the range of 93.4%–99.6% for all the analytes. The method was successfully applied to a bioequivalence study of 5 mg AML + 160 mg VAL + 12.5 mg HCTZ tablet formulation(test and reference) in 18 healthy Indian males under fasting. The mean log-transformed ratios of C max, AUC0–120 h and AUC0-inf and their 90% CIs were within 90.2%–102.1%. The assay reproducibility was demonstrated by reanalysis of 90 incurred samples.
文摘Amlodipine/valsartan(Aml/Val)single-pill combination(SPC)therapy has been widely used and studied in clinical practice in recent years.This article reviews the Chinese and English literature on the clinical use of Aml/Val SPC therapy in Chinese hypertensive patients.According to five studies concerning the efficacy and safety of this treatment,Aml/Val SPC therapy was more efficacious than monotherapy with valsartan,amlodipine,or the nifedipine gastrointestinal therapeutic system.This treatment showed greater blood pressure-lowering effects,a higher blood pressure control rate,and a higher response rate.Aml/Val SPC treatment was well tolerated,with adverse event rates similar to those of monotherapy with valsartan or amlodipine and significantly rarer adverse events compared with the nifedipine gastrointestinal therapeutic system.Aml/Val SPC is a highly efficacious and well-tolerated antihypertensive treatment in Chinese hypertensive patients.
文摘A simple, sensitive, and specific method was developed for simultaneous determination of Amlodipine besylate (AML), Valsartan (Vals) and Hydrochlorothiazide (HCT) by high performance liquid chromatography without previous separation. Satisfactory resolution was achieved using a RP-C18 chromatographic column, Phenomenex Kinetex (150 mm × 4.6 mm i.d) and a mobile phase consisting of acetonitrile-phosphate buffer (0.05 M) with pH 2.8 in the proportion of (40/60, v/v) at a flow rate 0.8 mL/min and the wavelength detection was 227 nm. The retention time for HCT, AML and VAls was 2.26, 3.16 and 11.19 min;respectively. The described method was linear over a range of 4-28 μg /ml, 5-40 μg /ml and 1-12 μg /ml for AML, Vals and HCT;respectively. The mean percent recoveries were 99.94%, 99.96% and 99.78% for AML, Vals and HCT;respectively. F-test and t-test at 95%con?dence level were used to check the intermediate precision data obtained under different experimental setups. The method could be used for analysis of combined dose tablet formulation containing AML, Vals, HCT as well as spiked human plasma.
文摘New HPLC method was developed for determination of amlodipine and valsartan in their binary mixture as a part of routine control of combined formulations. The method was validated to meet official requirements including selectivity, stability, linearity, precision and accuracy. Chromatography was carried out using a LiChrospher RP-18 column, a mixture containing acetonitrile, phosphate buffer of pH 3.5 and methanol (45:45:10, v/v/v) and new fluorescence detection at 255 nm for excitation and 448 nm for emission. The effect of methanol content, pH of the buffer, flow rate, detection wavelengths and column temperature was estimated in robustness study, according to a plan defined by the Plackett-Burman design. For identification of significant effects, both graphical and statistical methods were used. Ro-bustness for dissolution test was checked estimating the effects of paddle speed, temperature and pH of dissolution medium. The method was proved to complying with all official guidelines. Therefore, it is suitable for determination of amlodipine and valsartan in their binary mixtures for different analytical and pharmaceutical purposes.
