دراسة ثرموديناميكية وحركية للقياس الطيفي لهيدروكسي كلوروكين و لوبينافير

Thermodynamic, Kinetic And Spectrophotometric Studies Of Hydroxychloroquine And Lopinavir

Abstract : This study tried to find a quick, easy and inexpensive spectral way to detect two kinds of drugs ( HCQ and LPV) in pharmacological formula through the reaction of reagent (2,4-Dinitrophenylhydrazin) (2,4-DNPHz) with the oxidizing agent (potassium periodate) (KIO4) in presence of drug in alkaline medium.
The results revealed a high absorption for drugs (HCQ and LPV ) at the wavelengths (332nm and 322nm) respectively, while the highest absorption of the reagent (2,4-DNPHz) at wavelengths (359nm). Moreover the highest absorptions of the azo dye product were at (620nm) and (482nm) respectively.
This study was conducted to find out that the optimized conditions were experimented to estimate two drugs. It was shown that the optimized concentration reagent of drug (HCQ) and (LPV) was equal to (0.0075M), and (0.005M) respectively. While the optimal volumes of the reagent were (1ml) and (1.25ml) respectively. And the optimized volume of oxidizing agent was (0.75 ml) for each drugs. while the optimized volume of the base solution were (0.5ml) and (1.5ml) of drugs (HCQ and LPV) respectively.
Added to that the effect of temperature and time were conducted, a higher absorbance was obtained when temperature was (25⁰C) for HCQ and (35⁰C) for LPV ,while at the best time it was obtained at (10min) for each drug for the stability of the azo dye product.
The sequence of addition for each drug, reagent (2,4-DNPHz), oxidizing agent (KIO4) and the base solution(NaOH) also studied .The best sequences added to drugs (HCQ) and (LPV) were ( 2,4-DNPHz + KIO4 + drug +NaOH ).
The calibration curve of the two drugs was constructed after establishing the optimal conditions, The calibration curves were constructed and subsequently the Beer’s law was obeyed within the concentration ranges of drugs (HCQ and LPV ) which were equal (2.5 – 22.5µg.ml-1 ). The molar absorptivity (Ɛ) values were (1048.28) L.mol-1 .cm-1, and (3143.75)L.mol-1 .cm-1 respectively, and the Sandellʼs sensitivity values were t (0.3205) and (0.20002) μg.cm2 .The Detection limit (D.L) value were (0.243) and (0.933) μg.ml-1.The %R.S.D value were (%1.44) , and (%1.12).the %Erel value were (%-0.012), and (%-0.2525) with a correlation coefficient (0.9978) and (0.9967) respectively.
The stoichiometry of the reaction between two drugs with the (2,4-DNPHz) reagent was by using the continuous variations and mole ratio methods respectively equal to (1:1) for each drug and the stability constant (Ksta) was (7.52×106) L.mol-1 for (HCQ) , while the stability constant (Ksta) of (LPV) was (2.818×106) L.mol-1 .
Interferences were studied. The results reveal no effect on the determination of the two drugs.This technique has been used to successfully identify the drug (HCQ) in pharmaceutical formulation. And also to determine of (LPV) in serum.
Enthalpy (∆H), entropy (∆S), and Gibbs free energy (∆G), among other thermodynamic characteristics, were also estimated. It was found that the reaction between the two drugs and (2,4-DNPHz) reagent was endothermic, Spontaneous, and more regular.
The activation energy of the reaction between the two drugs and (2,4-DNPHz) reagent was also calculated and its value was (143.6) and (203.8) J/mol respectively.
Finally, kinetics of the reaction were studied, It was found that the reaction was pseudo second order of the two drugs