In Vitro Dissolution Study of Acetylsalicylic Acid and Clopidogrel Bisulfate Solid Dispersions: Validation of the RP-HPLC Method for Simultaneous Analysis

Applied Sciences

Marko Krstić¹  Jadranka Odović¹  Dragana Vasiljević²  Maja Pašić-Kulenović³  Ehlimana Osmanović Omerdić³  Larisa Alagić-Džambić⁴ 

[1] Department of Analytical Chemistry, University of Belgrade—Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia;Department of Pharmaceutical Technology and Cosmetology, University of Belgrade—Faculty of Pharmacy, Vojvode Stepe 450, 11221 Belgrade, Serbia;Development and Registration Department, Bosnalijek d.d., Jukićeva 53, 71000 Sarajevo, Bosnia and Herzegovina;Quality Assurance and Quality Control Department, Bosnalijek d.d., Jukićeva 53, 71000 Sarajevo, Bosnia and Herzegovina;

关键词: clopidogrel bisulfate;    acetylsalicylic acid;    solid dispersion;    dissolution;    RP-HPLC;    validation;   

DOI  :  10.3390/app10144792

来源: DOAJ

【 摘 要 】

Solid dispersions were prepared via a solvent evaporation method, employing ethanol (96%, v/v) as solvent, with three different polymers as carrier: povidone, copovidone, and poloxamer 407. Previously developed reversed-phase HPLC (RP-HPLC) methods were modified and used for the simultaneous determination of acetylsalicylic acid and clopidogrel bisulfate and after release from solid dispersions. Chromatography was carried out on a C-18 column, with a mobile phase of acetonitrile–methanol–phosphate buffer pH 3.0, UV detection at 240 nm, and a run time of 6 min. The method was validated according to International Conference of Harmonisation guidelines and validation included specificity, accuracy, precision, linearity, robustness, limit of detection (LOD), and limit of quantification (LOQ). The method is specific for determination of acetylsalicylic acid and clopidogrel bisulfate. The linearity was provided in the concentration range 0.0275–0.1375 mg/mL for acetylsalicylic acid and 0.0200–0.1000 mg/mL for clopidogrel bisulfate, with a correlation coefficient (R² value) of 0.9999 for both active pharmaceutical ingredients (APIs). Accuracy was confirmed by calculated recoveries for acetylsalicylic acid (98.6–101.0%) and clopidogrel bisulfate (100.0–101.6%). The intra-day and the inter-day precision-calculated relative standard deviations are less than 1%, which indicates high precision of the method. The limits of detection and quantification for acetylsalicylic acid were 0.0004 and 0.0012 mg/mL, and for clopidogrel bisulfate 0.0002 mg/mL and 0.0007 mg/mL, respectively. Small variations in chromatographic conditions did not significantly affect qualitative and quantitative system responses, which proved robustness of method. The proposed RP-HPLC method was applied for simultaneous determination of clopidogrel bisulfate and acetylsalicylic acid from solid dispersions.

【 授权许可】

Unknown