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

Abstract

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.

Construction and Evaluation of a Graphene Oxide Functionalized Aminopropyltriethoxy Silane Surface Molecularly Imprinted Polymer Potentiometric Sensor for Dipyridamole Detection in Urine and Pharmaceutical Samples

“…Roya Mirzajani * ,a and Ehsan Arefiyan a one serious problem for the determination of the analyte is complicated in the preliminary procedures, such as extraction. 19 Despite the simplicity of spectrophotometric methods, they are not very sensitive and often subject to interference from other analytes. However, some of the other methods are expensive, time-consuming or have limited sensitivity.…”

Dipyridamole intervention of breast cell carcinogenesis

“…Although DPM is approved by the FDA to inhibit platelet aggregation and vasoconstriction in patients , our research reveals that DPM may be an optimal preventive agent capable of blocking breast cell carcinogenesis induced by various, unrelated carcinogens in an ER‐independent manner. DPM, at a non‐cytotoxic physiologically achievable dose of 10 nmol/L, is effective in blocking transient endpoints and constitutive cancer‐associated properties induced by a single exposure and cumulative exposures, respectively, to PhIP, NNK, and B[ a ]P. Our results, for the first time, lead us to suggest that DPM should be seriously considered as a chemopreventive agent to reduce the health risk of sporadic breast cancer associated with long‐term exposure to environmental carcinogens.…”

“…Continuing our search for preventive agents to protect breast cells from carcinogenesis, we used our model system to investigate the activity of dipyridamole (DPM) [2,6‐bis(diethanolamino)‐4,8‐dipiperidinopyrimido‐(5,4‐ d )‐pyrimidine]. DPM, an antioxidant and a synthetic inhibitor of phosphodiesterase (Figure ), is approved by the Food and Drug Administration (FDA) to inhibit platelet aggregation and vasoconstriction . DPM is able to enhance the cytotoxicity of anticancer agents, such as cisplatin, adriamycin, and 5‐fluorouracil, in various cell types .…”

Development and Validation for Related Substances of Tartaric Acid Base Pellets of Dipyridamole Modified Release Capsules by Using High Performance Liquid Chromatography

“…However, several methods were reported for determination of dipyridamole in combination with other drug [8][9][10]. Estimation of dipyridamole and its metabolites in human plasma by LC-MS and HPLC has been performed [10][11][12][13]. In this method, the reported impurities and degradation impurities which includes three newly identified potential degradant impurities in our drug product during force degradation studies.…”