An Alternative Colorimetric Method for the Determination of Chloramphenicol

PURPOSE : To develop a simple; cheap; fast; accurate; sensitive and precise colorimetric method that can be used for the determination of chloramphenicol. METHOD : Chloramphenicol was reduced in a mixture of glacial acetic acid and water using titanium (III) chloride at room temperature within 10 min. The reduced product was then heated for 20 min with p-dimethylaminobenzaldehyde to yield the final product whose absorbance was used for the determination of the concentration of chloramphenicol. Results obtained with this method were compared with those obtained with the microbiological assay of chloramphenicol. RESULT : The final product of the two step reaction was greenish - yellow in colour;; absorbed strongly in the visible region and obeyed Beer's law at ?[max]= 440 nm. The method developed was sensitive and accurately determined chloramphenicol in the presence of common excipients and in different dosage forms. There was statistically no significant difference (p less than 0.05) between the results with the method developed and those obtained with the microbiological assay of chloramphenicol. CONCLUSION: A simple; fast; cheap; precise; sensitive and accurate colorimetric method has been developed that could be routinely used for the determination of chloramphenicol in bulk drug and in different dosage forms. The advantage of the method is its speed and simplicity

Adsorption, distribution and elimination of chloroquine in the presence of aspirin when administered into rabbits.

The absorption, distribution and elimination of chloroquine were studied in rabbits upon oral administration of chloroquine with aspirin. The time-lag, half-life of absorption and absorption rate constant obtained in both cases were significantly different (P less than 0.01) whereas the half-life of elimination and the elimination rate constant were not significantly different (P greater than 0.01). The results showed that absorption was delayed when aspirin was simultaneously administered with chloroquine but the distribution and elimination of chloroquine were not affected by the presence of aspirin.

Plasma, whole blood and red blood cell kinetics of chloroquine after oral and parenteral administration in rabbits.

The pharmacokinetics of chloroquine were studied after single oral, intramuscular and intravenous administration of the drug in rabbits. Chloroquine concentration was monitored in plasma, whole blood and red blood cells and the pharmacokinetic parameters were determined from the plasma, whole blood and red blood cell concentration-time data. By whatever route the drug was administered, higher concentrations were reached in red blood cells and whole blood than in plasma, but the concentrations declined at the same rate in the three media thus giving similar half-lives. However, the plasma, or whole blood or red blood cell half-lives varied depending upon whether the drug was given orally, intramuscularly or intravenously. With each route of administration the area under the plasma concentration-time curve was less than that for whole blood which was in turn less than that for red blood cells.

Tissue and blood concentrations of chloroquine following chronic administration in the rat.

The antimalarial drug, chloroquine, is extensively distributed in tissue and slowly eliminated such that after a single dose, a plasma half-life of 3-5 days has been found (McChesney & McAuliff 1961; McChesney et al 1967). A peak tissue/plasma concentration ratio greater than 300 is obtained in many tissues and after a single dose the drug can be found in the liver and urine for up to five years (Gaudette & Coatney 1961; Rubin et al 1963; Zvaifler et al 1963). Chronic administration of chloroquine for the treatment of rheumatoid arthritis has revealed an ocular toxicity due to accumulation of the drug in the pigmented layers of the eye, particularly the choroid (Fuld & Horwish 1958; Fuld 1959). A more recent indication for chronic administration of chloroquine is in the prophylaxis of malaria, for which the drug is administered at a dose of 300-600 mg weekly to adults. The long term toxic effects of chloroquine when administered in this way are unknown but no ocular toxicity has been reported even after five years of such use. Since tissue toxicity and other untoward effects are largely determined by tissue stores (Fuld & Horwish 1958; Fuld 1959) and blood levels (Laaksonen et al 1974; Frisk-Holmberg et al 1979) of the drug, it is useful to know the changes occurring in tissue and plasma concentrations during chronic administration. Previous studies in animals have given conflicting results. McChesney et al (1965) found a steady increase in the tissue and plasma concentrations in rats throughout a 3-month period although the increase was fastest in the first month. Grundmann et al (1972) found that most rat tissues were saturated with chloroquine between the 10th and the 16th weeks. Plasma concentrations were not measured hence the effect of tissue saturation on blood levels was not determined, yet saturation of tissue stores would be expected to lead to a rapid increase in plasma concentration that could affect the pattern and incidence of adverse reactions to the drug. We have reinvestigated the uptake of chloroquine by rat tissues during chronic administration of the drug and in particular to relate the tissue levels to plasma concentrations.

Kinetics of the uptake and elimination of chloroquine in children with malaria.

1 Ten children with Plasmodium falciparum malaria were treated with 25 mg/kg chloroquine over 3 days and observed for 7 days. 2 Chloroquine was determined in the red blood cells and plasma, and the red blood cell/plasma chloroquine concentration ratio was correlated with the disappearance of the parasites from the blood. It was found that this ratio decreased with the disappearance of the parasites and remained almost steady after the parasites had disappeared completely from the blood. 3 The half-life (t1/2) and the elimination rate constant of the "terminal' elimination slope (lambda beta) of the plasma log concentration-time curve were estimated to be 135.9 +/- 9.92 h and 0.005 +/- 0.001 h-1 (s.d.) respectively. 4 The t1/2 and lambda beta calculated from the red blood cell log concentration-time curve were not significantly different from the corresponding values calculated from the plasma log concentration-time curve.

Kinetics of the distribution and elimination of chloroquine in the rat.

1. The distribution of chloroquine was studied in the tissues and blood of rat. 2. The time to peak concentration and the maximum concentration varied in various tissues and were higher than for plasma and red blood cells. 3. The tissue to plasma concentration ratio increased with time up to 144th hr for some tissues while this ratio was still increasing at the 168th hr for other tissues. 4. The values of beta estimated for the tissues were lower than those for plasma or red blood cells. The values differed from one another for the tissues but were similar for plasma and red blood cells.

The effect of protein-energy malnutrition on the absorption, distribution and elimination of chloroquine in the rat.

1. Protein-energy malnutrition was induced in young rats by feeding them a protein-deficient diet. 2. The kinetics of uptake and elimination of chloroquine in various tissues were compared in normal rats, malnourished rats, and malnourished rats after recovery from malnutrition. 3. In the blood, liver, spleen, heart, kidney and skeletal muscle, uptake of chloroquine was slower in malnourished than in normal rats. Chloroquine was also eliminated at a slower rate in malnourished rats. In the skin chloroquine was taken up to a greater extent in malnourished than in normal rats. 4. When malnourished rats were allowed to recover from their state of malnutrition, the uptake and elimination of chloroquine no longer differed from those of animals that had never been malnourished.

Chloroquine sensitivity of Plasmodium falciparum in Ibadan, Nigeria.

Thirty-five children with Plasmodium falciparum malaria were treated with 25 mg/kg chloroquine over three days and observed for seven days during which blood films were examined daily for malaria parasites. Asexual forms of P. falciparum which were present in the blood films of all the patients before commencing treatment disappeared rapidly from the blood so that by the third day no parasites were seen in the blood film. The blood films remained negative for the rest of the seven-day observation period. Plasma chloroquine determination in eight of the patients showed high blood levels during the first three days. The results do not confirm the suspicion of chloroquine-resistant P. falciparum in the area studied although RI level of resistance by WHO criteria was not excluded.