Determination of warfarin enantiomers and hydroxylated metabolites in human blood plasma by liquid chromatography with achiral and chiral separation

Locatelli, Igor; Kmetec, Vojko; Mrhar, Aleš; Grabnar, Iztok

doi:10.1016/j.jchromb.2004.12.024

Cited by 73 publications

(65 citation statements)

References 22 publications

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“…29 Samples were prepared using liquid/liquid extraction. To a 1.0 ml plasma sample, 50 ml of naproxen (100 mg/l) as internal standard and 0.7 ml sulfuric acid (1 mol/l) were added.…”

Section: Drug Assaymentioning

confidence: 99%

Influence of CYP2C9 polymorphisms, demographic factors and concomitant drug therapy on warfarin metabolism and maintenance dose

Herman¹,

et al. 2005

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Warfarin is an anticoagulant drug with narrow therapeutic index and high interindividual variability in dose requirement. S-warfarin is metabolized mainly by polymorphic cytochrome P450 (CYP) 2C9. We systematically quantified the influence of CYP2C9 genotype, demographic factors and concomitant drug treatment on warfarin metabolism and maintenance dose. The mean warfarin doses were lower in carriers of one (2.71 mg/day, 59 patients) and two polymorphic alleles (1.64 mg/day, 11 patients) than in carriers of two wild-type alleles (4.88 mg/day, 118 patients). Multiple regression analysis demonstrated that CYP2C9 genotype, age, concomitant treatment with warfarin metabolism inducers and lean body weight contributed significantly to interindividual variability in warfarin dose requirement (adjusted R 2 ¼ 0.37). The same factors, except for age, significantly influenced S-warfarin clearance (adjusted R 2 ¼ 0.42). These results can serve as a starting point for designing prospective studies in patients in the initiation phase of genotype-based warfarin therapy.

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“…29 Samples were prepared using liquid/liquid extraction. To a 1.0 ml plasma sample, 50 ml of naproxen (100 mg/l) as internal standard and 0.7 ml sulfuric acid (1 mol/l) were added.…”

Section: Drug Assaymentioning

confidence: 99%

Influence of CYP2C9 polymorphisms, demographic factors and concomitant drug therapy on warfarin metabolism and maintenance dose

Herman¹,

et al. 2005

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“…In rare cases, resistance towards Vitamin K antagonists is due to mutations in the Vitamin K epoxide reductase complex (VKORC1) [3,4]. If the warfarin concentration is high but therapeutic INR is not reached, a mutation in Several methods using high-performance liquid chromatography (HPLC) exist in the literature for the quantification of warfarin enantiomers in human plasma [5][6][7][8][9][10][11][12][13][14][15][16]. Many of these methods are suffering either from an inappropriate choice of internal standard or from laborious extraction procedures using solid phase extractions with or without liquid-liquid phase extractions.…”

Section: Introductionmentioning

confidence: 99%

A new high-performance liquid chromatographic method for determination of warfarin enantiomers

Osman¹,

Arbring

Lindahl³

2005

Journal of Chromatography B

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“…Further, the metabolic ratio was also calculated based on which the populations may be categories as poor, rapid and ultra-rapid metabolizers. 17,18 In our previous studies we have explained the metabolic profiling for proguanil oxidation by CYP2C19, CYP2C9 induction/inhibition by phenytoin and phenytoin toxicity. 19,20 In the present study the metabolic ratio was calculated and the patients were stratified based on the required daily dose of warfarin.…”

Section: Discussionmentioning

confidence: 99%

Estimation of plasma levels of warfarin and 7-hydroxy warfarin by high performance liquid chromatography in patients receiving warfarin therapy

Kumar¹,

Shewade²,

Parasuraman³

et al. 2013

Journal of Young Pharmacists

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a b s t r a c tWarfarin is one of the most commonly prescribed oral anticoagulant for prevention of thromboembolic events. The effect of this drug is measured by monitoring prothrombin time expressed as International Normalized Ratio (INR). In some cases, however, the measurement of plasma concentration of warfarin was emphasized. In the present study, reversed phase high performance liquid chromatography (HPLC) was used to estimate the plasma drug levels. A total of 185 patients were enrolled in this study. Five milliliter of venous blood was collected using sodium EDTA tubes for pharmacokinetic analysis. Solid phase extraction was used to recover the warfarin and it's metabolite from plasma using isopropanol and potassium phosphate buffer (40:60) mobile phase. Warfarin, 7-hydroxy warfarin and carbamazepine (internal standard) were separated on a C18 column and had the retention time 3.6 min, 2.9 min and 5.9 min, respectively. The assay was linear in warfarin concentration ranges of 0.1e5 mg/ml. The extraction recovery was found to be x85%. The mean plasma concentrations of warfarin and 7-hydroxy warfarin were found to be 3.47 AE 1.87 (SD) mg/ml, 1.25 AE 0.81 (SD) mg/ml, respectively. Through the present study the plasma concentrations of warfarin, 7-hydroxy warfarin and their metabolic ratio was determined. The assay was sensitive to follow warfarin pharmacokinetics in a patient with warfarin therapy for 3 months and above.

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Determination of warfarin enantiomers and hydroxylated metabolites in human blood plasma by liquid chromatography with achiral and chiral separation

Cited by 73 publications

References 22 publications

Influence of CYP2C9 polymorphisms, demographic factors and concomitant drug therapy on warfarin metabolism and maintenance dose

Influence of CYP2C9 polymorphisms, demographic factors and concomitant drug therapy on warfarin metabolism and maintenance dose

A new high-performance liquid chromatographic method for determination of warfarin enantiomers

Estimation of plasma levels of warfarin and 7-hydroxy warfarin by high performance liquid chromatography in patients receiving warfarin therapy

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