Ticlopidine quantification in human plasma by high‐performance liquid chromatography coupled to electrospray tandem mass spectrometry. Application to bioequivalence study

Borges, Ney Carter do Carmo; Mendes, Gustavo Duarte; Borges, Andr�; Oliveira, Sandro Evandir de; Barrientos‐Astigarraga, Rafael E.; Nucci, Gilberto De

doi:10.1002/jms.708

Cited by 14 publications

(17 citation statements)

References 14 publications

(10 reference statements)

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“…The liquid-liquid extraction method of Borges et al was adapted (20). One mL of each sample was introduced into a glass tube, followed by 15 µL of metoprolol tartrate (Sigma-Aldrich) as internal standard at a concentration of 15 µg/mL of and 200 µL of NaHCO 3 0.5 M. Samples were vortex-mixed for approximately 10 s. Ten mL of diethyl-ether were added to all tubes, which were shaken horizontally 30 min and then frozen for another 30 min at -80 ºC.…”

Section: Extraction Procedures For Carvedilolmentioning

confidence: 99%

Artificial Neural Network Modeling for Drug Dialyzability Prediction

Daheb¹,

Lipman²,

Hildgen³

et al. 2013

J Pharm Pharm Sci

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-Purpose. The purpose of this study was to develop an artificial neural network (ANN) model to predict drug removal during dialysis based on drug properties and dialysis conditions. Nine antihypertensive drugs were chosen as model for this study. Methods. Drugs were dissolved in a physiologic buffer and dialysed in vitro in different dialysis conditions (UFRmin/UFRmax, with/without BSA). Samples were taken at regular intervals and frozen at -20ºC until analysis. Extraction methods were developed for drugs that were dialysed with BSA in the buffer. Drug concentrations were quantified by high performance liquid chromatography (HPLC) or mass spectrometry (LC/MS/MS). Dialysis clearances (CLDs) were calculated using the obtained drug concentrations. An ANOVA with Scheffe's pairwise adjustments was performed on the collected data in order to investigate the impact of drug plasma protein binding and ultrafiltration rate (UFR) on CLD. The software Neurosolutions ® was used to build ANNs that would be able to predict drug CLD (output). The inputs consisted of dialysis UFR and the herein drug properties: molecular weight (MW), logD and plasma protein binding. Results. Observed CLDs were very high for the majority of the drugs studied. The addition of BSA in the physiologic buffer statistically significantly decreased CLD for carvedilol (p= 0.002) and labetalol (p<0.001), but made no significant difference for atenolol (p= 0.100). In contrast, varying UFR does not significantly affect CLD (p>0.025). Multiple ANNs were built and compared, the best model was a Jordan and Elman network which showed learning stability and good predictive results (MSE testing = 129). Conclusion. In this study, we have developed an ANN-model which is able to predict drug removal during dialysis. Since experimental determination of all existing drug CLDs is not realistic, ANNs represent a promising tool for the prediction of drug CLD using drug properties and dialysis conditions.

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Section: Extraction Procedures For Carvedilolmentioning

confidence: 99%

Artificial Neural Network Modeling for Drug Dialyzability Prediction

Daheb¹,

Lipman²,

Hildgen³

et al. 2013

J Pharm Pharm Sci

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“…HPLC methods using a chiral stationary phase have been reported for the analysis of carvedilol enantiomers 6,7 . The clean-up procedures for the extraction of carvedilol from biological matrix consist of protein precipitation 5,6,10,12 , solid-phase extraction (SPE) 2,3,9 , liquid-liquid extraction (LLE) 6,7,[11][12][13] , combinations of protein precipitation with SPE 4 or combinations of LLE with back-extraction 1,8 . Those methods use a large amount of biological samples (0.15-1.0 mL plasma or 2-5 mL urine samples) in order to obtain the high sensitivity or include time-consuming extraction procedures and/or relatively long run time.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Carvedilol and Its Metabolite in Human Plasma Using Liquid Chromatography Coupled with Tandem Mass Spectrometry

Janjanam¹,

Bimireddy²

2017

IJPTR

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: A rapid, sensitive and selective method for the determination of Carvedilol and its metabolite in human plasma was developed using liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Carvedilol, its metabolite 4-OH carvedilol and abacavir (internal standard) were extracted from human plasma by solid phase extraction technique (SPE) and analyzed on an Discovery column (C8, 50 × 4.6 mm, 5µ) with the mobile phase of acetonitrile -0.1% formic acid in water (70:30 v/v). The analytes were detected using an electro spray ionization tandem mass spectrometry in the multiple reaction monitoring mode. The standard curve was linear (r = 0.9998) over the concentration range of 0.5-100 ng/mL and 0.3-40 ng/mL for carvedilol and 4-OH carvedilol respectively. The lower limit of quantification for carvedilol was 0.5 ng/mL and 0.3 ng/mL for carvedilol and 4-OH carvedilol respectively using 500 µL plasma samples. The coefficient of variation and relative error for intra-and inter-assay at four QC levels were 3.37 to 9.53 %, 4.76 to 7.01% and 3.31 to 6.91%, 5.23 to 6.64 % respectively. The matrix effect for carvedilol, 4-OH carvedilol and abacavir were practically absent. The extraction recoveries of carvedilol, 4-OH carvedilol and abacavir were 78.90, 83.25 and 85.20%, respectively.

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“…Carvedilol has been quantified in biological fluids using high-performance liquid chromatography (HPLC) with fluorescence [1][2][6][7][8][9][10][11] or electrochemical detector [12], mass spectrometry [13][14][15], hydrophilic interaction liquid chromatography (HILIC) with tandem mass spectrometry [16], capillary electrophoresis-ultra violet detector [17] and gas chromatography (GC)-MS detector [18]. The clean-up procedures for the extraction of carvedilol from biological matrix has been carried out by protein precipitation [8][9]13,15], solid-phase extraction (SPE) [2,6,12], liquid-liquid extraction (LLE) [10,14,18], combinations of protein precipitation with SPE [7] or combinations of LLE with back-extraction [1,11].…”

Section: Introductionmentioning

confidence: 99%

“…The clean-up procedures for the extraction of carvedilol from biological matrix has been carried out by protein precipitation [8][9]13,15], solid-phase extraction (SPE) [2,6,12], liquid-liquid extraction (LLE) [10,14,18], combinations of protein precipitation with SPE [7] or combinations of LLE with back-extraction [1,11]. However, these methods used a large volume of biological fluids (0.15-1.0 ml plasma or 2-5 ml urine), time-consuming pre-treat procedures for LLE, SPE or derivatization steps and required a long run-time (20 min) to obtain high sensitivity.…”

Section: Introductionmentioning

confidence: 99%

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Rapid and Sensitive Carvedilol Assay in Human Plasma Using a High-Performance Liquid Chromatography with Mass/Mass Spectrometer Detection Employed for a Bioequivalence Study

Kim¹,

Lee²

2010

AJAC

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A method for the determination of carvedilol in human plasma was developed using a high-performance liquid chromatography with tandem mass spectrometer (HPLC-MS/MS). Plasma samples were deproteinized using acetonitrile and the supernatant was directly injected onto the HPLC column without any preparative steps. Chromatography was performed on a reversed-phase (C 18 ) column with isocratic mobile phase for 2 min. The calibration curve was linear over the range of 2 to100 ng/ml (R 2 > 0.9998) and the lower limit of quantitation (LLOQ) was 2 ng/ml. This method showed acceptable precision and accuracy, good recovery from the plasma matrix, and stability during the analytical procedures. When its application to the bioequivalence test of two carvedilol 25 mg tablet formulations in male healthy 28 volunteers, this validated analysis method was appropriate resulting in the bioequivalence of two formulations: no statistically significant difference was observed between the logarithmic transformed area under curve (AUC) and maximum plasma concentration (C max ) values of the two formulations. The 90% confidence interval for the ratio of the above mentioned two parameters were within the bioequivalence limit of 0.80-1.25. These results suggested that the HPLC-MS/MS analysis method developed was suitable for the carvedilol analysis in human plasma.

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Ticlopidine quantification in human plasma by high‐performance liquid chromatography coupled to electrospray tandem mass spectrometry. Application to bioequivalence study

Cited by 14 publications

References 14 publications

Artificial Neural Network Modeling for Drug Dialyzability Prediction

Artificial Neural Network Modeling for Drug Dialyzability Prediction

Analysis of Carvedilol and Its Metabolite in Human Plasma Using Liquid Chromatography Coupled with Tandem Mass Spectrometry

Rapid and Sensitive Carvedilol Assay in Human Plasma Using a High-Performance Liquid Chromatography with Mass/Mass Spectrometer Detection Employed for a Bioequivalence Study

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