Development and validation of a liquid chromatography–tandem mass spectrometry method for simultaneous determination of amlodipine, atorvastatin and its metabolites ortho-hydroxy atorvastatin and para-hydroxy atorvastatin in human plasma and its application in a bioequivalence study

Zhou, Ying; Li, Jie; He, Xiaomeng; Jia, Mengmeng; Liu, Mingzhou; Li, Huqun; Xiong, Zhengjiang; Fan, Yue; Li, Weiyong

doi:10.1016/j.jpba.2013.04.021

Cited by 46 publications

(32 citation statements)

References 19 publications

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“…For atorvastatin, study 1 included a 20 mg tablet dosed to 36 healthy volunteers (18–45 years old),50 study 2 included a 20 mg tablet dosed to 24 healthy subjects,51 study 3 included an 80 mg capsule dosed to 36 healthy subjects (20–50 years old),52 and study 4 included a 10 mg tablet dosed to 50 healthy volunteers 53…”

Section: Methodsmentioning

confidence: 99%

Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability

Dennison¹,

Smith²,

Badhan³

et al. 2017

DDDT

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Cardiovascular disease (CVD) is the leading cause of death among men and women worldwide. In CVD, hypertension and dyslipidemia commonly coexist and are managed through coadministration of amlodipine and atorvastatin, respectively. The case for fixed-dose combination (FDC) oral dosage forms and orally disintegrating tablet (ODT) technology to enhance outcomes and compliance is strong. This work follows the development and characterization of single and FDC ODTs containing amlodipine and atorvastatin, followed by bioequivalence comparison between these single and FDC formulations, using in vitro dissolution and Caco-2 apparent permeability (Papp) and in silico physiologically based pharmacokinetic modeling approaches. ODTs containing amlodipine (5 mg) and atorvastatin (10 mg) either alone or in combination rapidly disintegrated (<30 s) while displaying a radial crushing strength in excess of 100 N and friability ≤1%. In vitro dissolution test was performed in fasted and fed-state simulated intestinal fluid (FeSSIF) and analyzed using high-performance liquid chromatography. Dissolution profiles for single and FDC ODTs were compared using US FDA recommended difference (f1) and similarity (f2) factor testing for bioequivalence. In all cases, there was no difference in active pharmaceutical ingredient dissolution between single or FDC ODTs, with the exception of amlodipine in FeSSIF. Pharmacokinetic clinical trial simulations were conducted using Simcyp (Version 14), incorporating Papp and dissolution data. Simulated clinical trials in healthy volunteers showed no difference in bioavailability based on pharmacokinetic parameters between single and combination doses with either active pharmaceutical ingredient. An increase in Cmax and AUC for atorvastatin in fed subjects was attributed to extended transit along the gut lumen and reduced atorvastatin metabolism due to lower CYP3A4 expression at more distal small intestine absorption sites. The results demonstrated bioequivalence of an FDC ODT for amlodipine and atorvastatin, while highlighting several limitations of f1 and f2 bioequivalence testing and strengths of mechanistic pharmacokinetic modeling for oral drug absorption.

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Section: Methodsmentioning

confidence: 99%

Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability

Dennison¹,

Smith²,

Badhan³

et al. 2017

DDDT

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“…HPLC has been remained as a method of choice for determination of drugs alone or in ISSN: 2249-6041 (Print); ISSN: 2249-9245 (Online) combination with other drugs in the pharmaceutical formulations (Bhimavarapu et al 2011;Basaveswara Rao et al 2012;Chhabra and Banerjee, 2013;Patwari et al 2014;Singh and Dahiya, 2014;Shrestha et al 2016). Till date, several methods have been reported for the determination of OLM and AML either individually or in combination with other drugs in plasma with LC-MS/ MS and HPLC-UV (Liu et al 2007;Chen et al 2008;Liu et al 2010;Sengupta et al 2010;Zhou et al 2013). Two methods reported for combination of these drugs for simulation determination in plasma are one each on HPLC-UV and LC-MS/MS (Shah et al 2012;Qi et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Determination of Amlodipine and Olmesartan in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry and Its Application in Pharmacokinetic Study

Jain¹,

YR²,

Kishore³

2016

Bull. Pharm. Res

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The present study describes a sensitive, specific and rapid method based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of amlodipine (AML) and olmesartan (OLM) in human plasma by using amlodipine D4 (IS1) and olmesartan D6 (IS2) as internal standards. Plasma samples were extracted by solid-phase extraction (SPE). The method was validated over parameters like selectivity, matrix effect, sensitivity, specificity, linearity, precision and accuracy, various stabilities in plasma, recovery and reinjection reproducibility. During the validation, inter and intra-batch precision were less than 15% and the accuracy was within 85-115%. Extraction recoveries were 75.30%, 81.41%, 79.19% and 81.72% for AML, OLM, IS1 and IS2 respectively. The method was applied to the pharmacokinetic study of OLM and AML in healthy subjects following a single oral dose of OLM and AML 40 mg/10 mg.

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“…AMB is available in 2.5, 5 and 10 mg oral dose alone and in combination with other drugs with 10 mg/day being the maximum daily dose. AMB orally disintegrating tablet is official in the United States Pharmacopoeia [9]. Literature survey revealed voltametric determination of AMB in human urine and pharmaceuticals [10].…”

Section: Introductionmentioning

confidence: 99%

Development and Application of Rp-Hplc Method for Dissolution Study of Oral Formulations Containing Amlodipine Besylate

Pawar¹,

Yadav²

2015

Pharm Anal Acta

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In the present analytical study a rapid, robust and specific reversed-phase HPLC method has been developed and validated for quantitative estimation of amlodipine besylate in the dissolution study of oral films by direct injections of aqueous solutions. The study involved isocratic elution of amlodipine besylate in Zorbax ® Eclipse XDB-C18 analytical column using buffer (0.7 % aqueous triethylamine adjusted to pH 3.0 with orthophosphoric acid) and methanol in the ratio of 40:60 (v/v). The aqueous solutions were analysed at a flow rate of 1.0 ml/min at 239 nm. The method presented linearity (r 2 = 0.999) in the concentration range 20-150 µg/ml. The result indicated good recoveries ranging from 98.06% to 99.22%. The method showed good precision with % Relative standard deviation value less than 2. All the validation parameters were within the acceptance range. The developed method can be successfully employed for in-vitro dissolution and routine analysis of formulations containing Amlodipine besylate.

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Development and validation of a liquid chromatography–tandem mass spectrometry method for simultaneous determination of amlodipine, atorvastatin and its metabolites ortho-hydroxy atorvastatin and para-hydroxy atorvastatin in human plasma and its application in a bioequivalence study

Cited by 46 publications

References 19 publications

Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability

Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability

Simultaneous Determination of Amlodipine and Olmesartan in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry and Its Application in Pharmacokinetic Study

Development and Application of Rp-Hplc Method for Dissolution Study of Oral Formulations Containing Amlodipine Besylate

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