Development and validation of high-throughput liquid chromatography–tandem mass spectrometric method for simultaneous quantification of Clopidogrel and its metabolite in human plasma

S, Raghunadha Reddy; Rao.Divi, Koteswara; Chandiran, Irisappan Sarath; Jayaveera, K. N.; Naidu, YK; Reddy, Murali

doi:10.1016/j.jchromb.2009.12.026

Cited by 15 publications

(3 citation statements)

References 14 publications

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“…However, the linearity and precision of TPT in the plasma samples were not within the acceptable limits. The matrix effect corresponds to the residual components of the biological matrix that alters mass spectrometry response, decreases method robustness, increases method variability and leads to poor limits of detection (Reddy et al ., ). We obtained better results using the Ostro TM sorbent plate for preparing the plasma samples.…”

Section: Resultsmentioning

confidence: 97%

Development and validation of a liquid chromatography–tandem mass spectrometry method for topotecan determination in beagle dog plasma and its application in a bioequivalence study

Shi

Wan

et al. 2013

Biomedical Chromatography

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Topotecan (TPT) is an important anti-cancer drug that inhibits topoisomerase I. A sensitive and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method that potentially determines TPT in beagle dog plasma is needed for a bioequivalence study of TPT formulations. We developed and validated LC-MS/MS to evaluate TPT in beagle dog plasma in terms of specificity, linearity, precision, accuracy, stability, extraction recovery and matrix effect. Plasma samples were treated with an Ostro(TM) sorbent plate (a robust and effective tool) to eliminate phospholipids and proteins before analysis. TPT and camptothecin (internal standard) were separated on an Acquity UPLC BEH C18 column (1.7 µm, 2.1 × 50 mm) with 0.1% formic acid and methanol as the mobile phase at a flow rate of 0.25 mL/min. TPT was analyzed using positive ion electrospray ionization in multiple-reaction monitoring mode. The obtained lower limit of quantitation was 1 ng/mL (signal-to-noise ratio > 10). The standard calibration curve for TPT was linear (correlation coefficient > 0.99) at the concentration range of 1-400 ng/mL. The intra-day and inter-day precision, accuracy, stability, extraction recovery and matrix effect of TPT were within the acceptable limits. The validated method was successfully applied in a bioequivalence study of TPT in healthy beagle dogs.

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Section: Resultsmentioning

confidence: 97%

Development and validation of a liquid chromatography–tandem mass spectrometry method for topotecan determination in beagle dog plasma and its application in a bioequivalence study

Shi

Wan

et al. 2013

Biomedical Chromatography

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“…The proposed analytical method to measure clopidogrel and SA concentrations simultaneously has lower LOQ values for CAM and SA than previously reported methods , indicating higher sensitivity for simultaneous detection of clopidogrel and CAM concentrations. The non‐significant degradation of clopidogrel and its metabolite observed in our study was also observed by other investigators . This characteristic is important to ensure accurate and precise results in therapeutic monitoring.…”

Section: Discussionmentioning

confidence: 75%

ABCC3 Polymorphisms and mRNA Expression Influence the Concentration of a Carboxylic Acid Metabolite in Patients on Clopidogrel and Aspirin Therapy

Luchessi

Concheiro

Germano

et al. 2017

Basic Clin Pharma Tox

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Acetylsalicylic acid (ASA) and clopidogrel combined therapy has been reported to be beneficial in patients with acute coronary syndrome (ACS). Antiplatelet drug resistance, especially to clopidogrel, is a multifactorial phenomenon that affects a large number of ACS patients. The genetic contribution to this drug response is not fully elucidated. We investigated the relationship of ABC-type efflux subfamily C member 3 (ABCC3) polymorphisms and mRNA expression with plasma concentrations of clopidogrel, salicylic acid (SA) and a carboxylic acid metabolite (CAM). Clopidogrel, CAM and SA plasma concentrations were measured simultaneously by liquid chromatography-tandem mass spectrometry (LCMS/MS) from 83 ACS patients undergoing percutaneous coronary intervention. ABCC3 (rs757421, rs733392 and rs739923) and CYP2C19*2 (rs4244285) polymorphisms as well as mRNA expression were evaluated. A positive correlation was found between CAM concentrations and ABCC3 mRNA expression (r = 0.494, p < 0.0001). Patients carrying genotype AA (rs757421 variant) had higher CAM concentrations and ABCC3 mRNA expression as compared to those of GG + GA carriers (p = 0.017). A multiple linear regression analysis revealed that ABCC3 mRNA expression (p = 0.017), rs757421 AA genotype (p = 0.001), blood collection time (p = 0.018) and clopidogrel dose (p = 0.001) contributed to the concentration of CAM. No associations were observed for the CYP2C19*2 polymorphism. These results suggest that up-regulation of ABCC3 mRNA expression leads to increased plasma CAM levels through MRP3-mediated cell efflux. The ABCC3 rs757421 polymorphism may contribute to gene expression. Therefore, ABCC3 may be a potential biomarker for the response to clopidogrel.

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“…Some LC−MS/MS assays for quantification of clopidogrel or its metabolites have been reported. Several methods were developed to simultaneously quantify clopidogrel and its main metabolite clopidogrel carboxylic acid [9] , [10] , [11] , [12] , [13] , [14] : one work was established to quantify clopidogrel and its derivatized active thiol metabolite [15] ; another study was reported for the simultaneous determination of clopidogrel, its main metabolite and derivatized isomers of thiol metabolite [16] ; and one paper presented the simultaneous quantification of clopidogrel, its main metabolite and the newly described acyl glucuronide metabolite [17] . To the best of our knowledge, no methods have been reported for quantification of 2-oxo-clopidogrel in human plasma yet.…”

Section: Introductionmentioning

confidence: 99%

Development of an LC−MS/MS method for determination of 2-oxo-clopidogrel in human plasma

Song

Hang

2015

Journal of Pharmaceutical Analysis

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A sensitive and selective liquid chromatography–tandem mass spectrometric (LC−MS/MS) method was established to determine 2-oxo-clopidogrel, a crucial intermediate metabolite in human plasma. A chromatographic separation was performed on a Sapphire C18 column following a liquid–liquid extraction sample preparation with methyl t-butyl ether. Detection was carried out on a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) with an electrospray ionization (ESI) mode. The method was validated in terms of specificity, accuracy, precision and limit of quantification. The calibration curves ranged from 0.50 to 50.0 ng/mL with good linearity. The stability was fully validated with addition of 1,4-dithio-DL-threitol (DTT) into the plasma sample prior to and in the preparation procedure. The validated method was proved to be suitable for use in pharmacokinetic study after single oral administration of 75 mg clopidogrel tablets in human subjects, which could make contribution to intensive study of the clinical drug–drug interactions of clopidogrel and individual treatment.

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Development and validation of high-throughput liquid chromatography–tandem mass spectrometric method for simultaneous quantification of Clopidogrel and its metabolite in human plasma

Cited by 15 publications

References 14 publications

Development and validation of a liquid chromatography–tandem mass spectrometry method for topotecan determination in beagle dog plasma and its application in a bioequivalence study

Development and validation of a liquid chromatography–tandem mass spectrometry method for topotecan determination in beagle dog plasma and its application in a bioequivalence study

ABCC3 Polymorphisms and mRNA Expression Influence the Concentration of a Carboxylic Acid Metabolite in Patients on Clopidogrel and Aspirin Therapy

Development of an LC−MS/MS method for determination of 2-oxo-clopidogrel in human plasma

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