This study presents a comparative drugprotein, in vitro, binding profile of sodium aurothiomalat... more This study presents a comparative drugprotein, in vitro, binding profile of sodium aurothiomalate and auranofin. It was found that about 40% of total protein-bound gold is attached to albumin after incubation of aurothiomalate with whole blood for 24 h and about 29% of it was with ...
Summary: The hydrolysis of acetylsalicylic acid (ASA) and copper (II)-acetylsalicylate (CAS) was ... more Summary: The hydrolysis of acetylsalicylic acid (ASA) and copper (II)-acetylsalicylate (CAS) was investigated by using a validated RP-HPLC method. Acetylsalicylic acid was hydrolyzed to (SA), where as CAS was hydrolyzed to ASA, SA, copper salicylate (CS), copper acetate and acetic acid. Comparison of hydrolysis was carried out by monitoring the concentration of SA, one of common hydrolysis product. The hydrolysis study was done in phosphate buffer solution in pH range from 311. The study was carried out at constant temperature to evaluate the effect of pH on both drugs. It was found that the hydrolysis rate of both drugs was same at pH value ranging from 3-11 as calculated from the Kapp and K values. However, there is a slight difference in the degradation of ASA and CAS as revealed from F-test. Results have indicated that CAS first hydrolyzes to acetylsalicylic acid which further hydrolyzes to SA, therefore availability of acetylsalicylic acid is increased.
This study presents a comparative drug-protein, in vitro, binding profile of sodium aurothiomalat... more This study presents a comparative drug-protein, in vitro, binding profile of sodium aurothiomalate and auranofin. It was found that about 40% of total protein-bound gold is attached to albumin after incubation of aurothiomalate with whole blood for 24 h and about 29% of it was with alpha(1)-globulin and the least amount was found with gamma-globulin (6.1%). On the other hand, approximately 84% of the protein-bound auranofin gold attached to globulins of which 51% was found with beta-globulin band. It was almost equally distributed among albumin, alpha(2)-globulin and gamma-globulin, and showed least affinity for alpha(1)-globulin. The gold analyses were performed by standardless instrumental neutron activation method duly validated by use of an established atomic absorption method. The results of this study explain to some extent the difference in, in vivo, pharmacokinetics and pharmacodynamics of the two drugs.
Interaction of auricyanide, an important metabolite of anti-arthritic gold-based drug auranofin, ... more Interaction of auricyanide, an important metabolite of anti-arthritic gold-based drug auranofin, was studied in vitro with a pharmacologically active ligand N-acetylcysteine with a view to understand reactivity of gold in vivo. Formation of reduction product aurocyanide occurred through mono-and diN -acetylcysteine-substituted intermedi-ates. The product and intermediates were identified and monitored spectrophotometrically and by electrospray ionization mass spectrometry. This study suggests successive substitution with N-acetylcysteine through trans effect. At equimolar concentrations of auricyanide and N-acetylcysteine, only mono-substituted mixed-ligand complex was formed. Substitution of the data obtained to various kinetic models suggested that the reaction orders are 0.6 in terms of N-acetylcysteine, 1.5 in terms of auricyanide, and 2 overall. The intermediates detected in this work may help to synthesize more effective and less toxic gold drugs.
This study presents a comparative drugprotein, in vitro, binding profile of sodium aurothiomalat... more This study presents a comparative drugprotein, in vitro, binding profile of sodium aurothiomalate and auranofin. It was found that about 40% of total protein-bound gold is attached to albumin after incubation of aurothiomalate with whole blood for 24 h and about 29% of it was with ...
Summary: The hydrolysis of acetylsalicylic acid (ASA) and copper (II)-acetylsalicylate (CAS) was ... more Summary: The hydrolysis of acetylsalicylic acid (ASA) and copper (II)-acetylsalicylate (CAS) was investigated by using a validated RP-HPLC method. Acetylsalicylic acid was hydrolyzed to (SA), where as CAS was hydrolyzed to ASA, SA, copper salicylate (CS), copper acetate and acetic acid. Comparison of hydrolysis was carried out by monitoring the concentration of SA, one of common hydrolysis product. The hydrolysis study was done in phosphate buffer solution in pH range from 311. The study was carried out at constant temperature to evaluate the effect of pH on both drugs. It was found that the hydrolysis rate of both drugs was same at pH value ranging from 3-11 as calculated from the Kapp and K values. However, there is a slight difference in the degradation of ASA and CAS as revealed from F-test. Results have indicated that CAS first hydrolyzes to acetylsalicylic acid which further hydrolyzes to SA, therefore availability of acetylsalicylic acid is increased.
This study presents a comparative drug-protein, in vitro, binding profile of sodium aurothiomalat... more This study presents a comparative drug-protein, in vitro, binding profile of sodium aurothiomalate and auranofin. It was found that about 40% of total protein-bound gold is attached to albumin after incubation of aurothiomalate with whole blood for 24 h and about 29% of it was with alpha(1)-globulin and the least amount was found with gamma-globulin (6.1%). On the other hand, approximately 84% of the protein-bound auranofin gold attached to globulins of which 51% was found with beta-globulin band. It was almost equally distributed among albumin, alpha(2)-globulin and gamma-globulin, and showed least affinity for alpha(1)-globulin. The gold analyses were performed by standardless instrumental neutron activation method duly validated by use of an established atomic absorption method. The results of this study explain to some extent the difference in, in vivo, pharmacokinetics and pharmacodynamics of the two drugs.
Interaction of auricyanide, an important metabolite of anti-arthritic gold-based drug auranofin, ... more Interaction of auricyanide, an important metabolite of anti-arthritic gold-based drug auranofin, was studied in vitro with a pharmacologically active ligand N-acetylcysteine with a view to understand reactivity of gold in vivo. Formation of reduction product aurocyanide occurred through mono-and diN -acetylcysteine-substituted intermedi-ates. The product and intermediates were identified and monitored spectrophotometrically and by electrospray ionization mass spectrometry. This study suggests successive substitution with N-acetylcysteine through trans effect. At equimolar concentrations of auricyanide and N-acetylcysteine, only mono-substituted mixed-ligand complex was formed. Substitution of the data obtained to various kinetic models suggested that the reaction orders are 0.6 in terms of N-acetylcysteine, 1.5 in terms of auricyanide, and 2 overall. The intermediates detected in this work may help to synthesize more effective and less toxic gold drugs.
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