High-performance liquid chromatographic analysis of dipyridamole in plasma and whole blood

Wolfram, Katherine M.; Bjornsson, Thorir D.

doi:10.1016/s0378-4347(00)81398-5

Cited by 44 publications

(8 citation statements)

References 3 publications

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“…Samples for serum TxB2 measurements were obtained preceding initiation of drug therapy, and I h after the morning dose on the second day of oral drug administration. Concentrations of dipyridamole in plasma were determined by using a sensitive and specific high performance liquid chromatography (HPLC) method based on paired-ion chromatography and fluorescence detection (7). This assay has been used in two recent clinical studies to characterize the pharmacokinetics of dipyridamole (8,9).…”

Section: Methodsmentioning

confidence: 99%

Effects of platelet-modifying drugs on arterial thromboembolism in baboons. Aspirin potentiates the antithrombotic actions of dipyridamole and sulfinpyrazone by mechanism(s) independent of platelet cyclooxygenase inhibition.

Hanson¹,

Harker²,

Bjornsson³

1985

J. Clin. Invest.

120

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To resolve questions of drug actions, efficacy, and interactions for platelet-modifying agents used clinically, we have compared the relative capacities and mechanisms of aspirin, dipyridamole, sulfinpyrazone, and dazoxiben to prevent arterial thromboembolism in a baboon model. In 136 studies the agents were given twice daily by oral administration both singly and in combination. The antithrombotic efficacy of a given therapy was determined by its capacity to interrupt steady-state platelet utilization induced by thrombogenic arteriovenous cannulae.When given alone, dipyridamole and sulfinpyrazone reduced the rate at which platelets were utilized by thrombus formation in a dose-dependent manner with essentially complete interruption by dipyridamole at 10 mg/kg per d. In contrast, neither aspirin (2-100 mg/kg per d) nor dazoxiben (20-100 mg/kg per d) decreased cannula platelet consumption detectably despite the striking reduction in the capacity of platelets to produce thromboxane B2. However, aspirin, but not dazoxiben, potentiated the antithrombotic effects of dipyridamole and sulfinpyrazone in a dose-dependent fashion without changing the pharmacokinetics for any of the agents. Complete potentiation required aspirin at 20 mg/kg per d to be given with each dose of dipyridamole. Because dazoxiben's blockade of platelet thromboxane A2 production was not associated with antithrombotic potentiation, and because complete potentiation by aspirin required a dose that fully inhibited vascular production of prostaglandin I2 (PGI2), we conclude that aspirin's potentiating effect on dipyridamole is independent of PGI2 production or inhibition of thromboxane A2 formation. In addition, because frequent repeated and synchronous dosing of aspirin was necessary, aspirin's potentiating effects appear to be produced by mechanism(s) unrelated to its potent, irreversible inhibition of platelet cyclooxygenase.

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Section: Methodsmentioning

confidence: 99%

Effects of platelet-modifying drugs on arterial thromboembolism in baboons. Aspirin potentiates the antithrombotic actions of dipyridamole and sulfinpyrazone by mechanism(s) independent of platelet cyclooxygenase inhibition.

Hanson¹,

Harker²,

Bjornsson³

1985

J. Clin. Invest.

120

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“…However, these methods often suffer from disadvantages, including the lack of specificity inherent in nonchromatographic analytical methods for drugs in biological samples (Steyn, 1979), low sensitivity or long running time (Pedersen, 1979;Huang et al, 2003;Liu and Smith, 1996;Yamamoto et al, 2006;Siebert and Bochner, 1987;Kunkel and Watzig, 1999) and complex and time-consuming analytical procedures and/or derivatization (Steyn, 1979;Mongillo and Paul, 1997;Pirker et al, 2004). Some methods (Wolfram and Bjornsson, 1980) which can satisfy the quantitation of one drug in biological fluids selectively and sensitively cannot be applied to simultaneous determination of the two drugs.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of dipyridamole and salicylic acid in human plasma by high performance liquid chromatography‐mass spectrometry

Wang¹,

Xu²,

Zhang³

et al. 2007

Biomedical Chromatography

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A sensitive, rapid and simple high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) method for simultaneous determination of dipyridamole and salicylic acid in human plasma has been developed and validated. After the addition of diazepam and rosiglitazone as internal standard (IS), plasma samples were prepared by liquid-liquid extraction followed by an isocratic elution with methanol:2 mM ammonium acetate buffer (pH 4.25; 70/30, v/v) on a Shimadzu VP-ODS C(18) column (5 microm, 150 x 2.0 mm I.D.). Detection was performed on a quadrupole mass spectrometer with ESI interface operating in the positive-ion mode for dipyridamole and negative-ion mode for salicylic acid. Calibration curves were linear (r(2) > 0.99) over the concentration range 10-2500 ng/mL for dipyridamole and 30-4000 ng/mL for salicylic acid with acceptable accuracy and precision, respectively. The intra- and inter-batch precisions were less than 15% of the relative standard deviation. The limits of detection of dipyridamole and salicylic acid were 1 and 15 ng/mL, respectively. The validated HPLC-ESI-MS method was successfully applied to a preliminary pharmacokinetic study of fixed-dose combination of sustained-release dipyridamole/aspirin in Chinese healthy male volunteers.

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“…Analytical methods have been reported for quantitative determination of dipyridamole in biological fl uid, such as thin-layer chromatography with fl uoridensitometric and spectrofl uorimetric method (Steyn, 1979) and HPLC with ultraviolet or fl uorescence detection (Barberi et al, 1991;Wolfram and Bjornsson, 1980;Williams et al, 1981). However, these methods often suff er from some disadvantages such as lack of specifi city, low sensitivity, poor reproducibility, long chromatographic running time and time-consuming sample preparation.…”

Section: Introductionmentioning

confidence: 99%

Quantitative determination of dipyridamole in human plasma by high‐performance liquid chromatography–tandem mass spectrometry and its application to a pharmacokinetic study

Qin

et al. 2009

Biomedical Chromatography

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Dipyridamole is a classic platelet inhibitor which has been a key medicine in clinical therapy of thrombosis and cerebrovascular disease. A rapid, selective and convenient method using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed for determination of dipyridamole in human plasma. After protein precipitation of 200 microL plasma with methanol, dipyridamole and diazepam (internal standard) were chromatographed on an Ultimate XB-C(18) (50 x 2.1 mm i.d, 3 microm) column with the mobile phase consisting of methanol-ammonium acetate (5 mM; 80 : 20, v/v) at a flow rate of 0.25 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring mode via positive eletrospray ionization source (ESI(+)). The retention times of dipyridamole and diazepam were 1.4 and 1.2 min, respectively. The method was validated over a concentration range of 0.0180-4.50 microg/mL (r(2) > or = 0.99) with a lower limit of quantitation (LLOQ) of 0.0180 microg/mL for dipyridamole. The intra- and inter-day precisions (RSD) of the assay at all three QC levels were 1.6-12.7% with an accuracy (RE) of -4.3-1.9%, which meets the requirements of the FDA guidance. The HPLC-MS/MS method herein described was proved to be suitable for pharmacokinetic study of sustained-release dipyridamole tablet in volunteers after oral administration.

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High-performance liquid chromatographic analysis of dipyridamole in plasma and whole blood

Cited by 44 publications

References 3 publications

Effects of platelet-modifying drugs on arterial thromboembolism in baboons. Aspirin potentiates the antithrombotic actions of dipyridamole and sulfinpyrazone by mechanism(s) independent of platelet cyclooxygenase inhibition.

Effects of platelet-modifying drugs on arterial thromboembolism in baboons. Aspirin potentiates the antithrombotic actions of dipyridamole and sulfinpyrazone by mechanism(s) independent of platelet cyclooxygenase inhibition.

Simultaneous determination of dipyridamole and salicylic acid in human plasma by high performance liquid chromatography‐mass spectrometry

Quantitative determination of dipyridamole in human plasma by high‐performance liquid chromatography–tandem mass spectrometry and its application to a pharmacokinetic study

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