Pharmacokinetic Study And Metal Ions Test Of Dipyridamole Preparations Based On Cloud Point Extraction

It was found that the cloud point extraction technology(CPE)had some advantages through a large number of literature search.CPE is safety,low cost,low toxicity and easy disposal of surfactanteasy disposal.But there are few reported that CPE is used in dipyridamole preparation research in literature.In this paper,the pharmacokinetics of dipyridamole tablets and ginkgo leaf extract and dipyridamole injectio n were studied based on CPE for the first time.At the same time,trace lead and potassium were quantitative analysis in ginkgo leaf extract and dipyridamole injection.1.Dipyridamole tablet is widely used in clinical.The extraction of dipyridamole from biological samples based on CPE is not involved in literature.CPE-HPLC was developed for the determination of dipyridamole in rat plasma after oral administration dipyridamole tablets.The non-ionic surfactant Triton X-114 was chosen as the extract medium.Variable parameters of affecting the CPE efficiency were evaluated and optimized.Dipyridamole were extracted from rat plasma after adding 1 mL of 5%(w/v)Triton X-114 in the presence of 1.5 mol�L-1 NaOH,the mixture was placed in an bath at 50? for 20 mins.Separation was carried out on a reversed-phase Zorbax SB-C18 column(250 � 4.6 mm,5 ?m)at 30? with a detection wavelength at 292 nm.Under the optimum conditions,the assay was linear over the range of 0.1-20.0 ?g�mL-1,the extraction recoveries were more than 83.1%,the accuracies were within �9.7%,and the intra-and inter-day precisions were less than �12.6% in all cases.After strict validation,the method was successfully applied to the pharmacokinetic study of dipyridamole in rat after oral administration dipyridamole tablets.2.Ginkgo leaf extract and dipyridamole injection is a compound preparations of dipyridamole.The determination of dipyridamole of Ginkgo leaf extract and dipyridamole injection in biological samples based on CPE is not involved in the literature.CPE coupled to liquid chromatography-electrospray ionization-tandem mass spectrometry(LC-ESI-MS/ MS)was developed for analysis of dipyridamole in rat plasma after intravenous administration of ginkgo leaf extract and dipyrida mole injection.The non-ionic surfactant Triton X-114 was chosen as the extract medium.Variable parameters of affecting the CPE efficiency,such as the amount of Triton X-114,NaOH concentration and equilibration temperature,were evaluated and optimized.Dipyridamole were extracted from rat plasma after adding 300 ?L of 7%(w/v)Triton X-114 in the presence of 2 mol�L-1 NaOH,and the mixture was placed in an bath at 55? for 20 min.The separation was carried out on a SunFire C18(150 mm � 2.1 mm,5 ?m),the mobile phase consisted of 0.1% formic acid-acetonitrile was used as gradient elution,the flow rate was 0.2 mL?min-1,and the column temperature was kept at 40?.The electrospray ionization interface was set in the positive mode.Quantification was performed in the multiple reaction monitoring mode.The transitions of m/z 505.3 ? 385.2 was for dipyridamole and m/z 285.0 ? 154.0 was for diazepam,respectively.Under the optimum conditions,calibration curve was linear over the range of 10.0-2500.0 ng�mL-1 and the lower limit of quantification(LLOQ)was 10 ng�mL-1.The extraction recoveries were all more than 80.9%,the accuracies were within �3.6%,and the intra-and inter-day precisions were less than �7.24% in all cases.After strict validation,the method was successfully applied to the pharmacokinetic study of dipyridamole in rat plasma after intravenous administration of ginkgo leaf extract and dipyridamole injection.3.Lead is harmful to people and the detection of metallic lead is of great significance.A method based on CPE was developed for determination of trace Pb in ginkgo leaf extract and dipyridamole injection by Graphite Furnace Atomic Absorption Spectrometry(GFAAS).The non-ionic surfactant Triton X-114 was chosen as the extract medium,1% NH4H2PO4 was chosen as matrix modifer,and trace Pb in the form of a coordination complex with dithizone was separated and enriched from the sample solution.Trace lead were extracted from ginkgo leaf extract and dipyridamole injection after adding 0.7 mL of 20 g�L-1 Triton X-114 in the presence of 1�10-3 mol�L-1 dithizone solution,and the mixture was placed in an bath at 50? for 15 mins.The analysis parameters of instrument with detection wavelength of 283.3 nm,lamp current of 10 mA,and spectral pass band width of 1.0 nm.Under the optimal conditions,Pb was enriched by 10 folds,the limit of detection of Pb was 0.0875 ng�mL-1,values of recovery were 99.4%-104.4%,and calibration curves were linear(r=0.9996)over the range of 0.1-30.0 ng�mL-1.The proposed method was successfully applied to the determination of trace Pb in ginkgo leaf extract and dipyridamole injection.4.Detction of potassium is an important index in quality standards of an intravenous injection.Flame atomic spectrophotomety was developed for the determination of potassium in ginkgo leaf extract and dipyridamole injection.The analysis parameters of instrument with detection wavelength of 766.5 nm,working current of 6 mA,slit of 0.5 nm,and gas flow rate of 1.8 L�min-1.Calibration curves were linear over the range of 0.2-1.6 ?g�mL-1(r=0.9996).The mean recovery was 101.8% with RSD of 2.3%.The method is simple,rapid,accurate and reliable.After validation,it can be used for quality control of ginkgo leaf extract and dipyridamole injection.