Primaquine antimalarial

PRIMAQUINE ANTIMALARIALS -ARTEMETHERWITH LUMEFANTRINE Risk of arrhythmias Additive effect Avoid co-administration... 

Finally the aminoquinoline bearing a primary amine at the terminal carbon atom of the side chain is itself an effective antimalarial drug. Ring opening of 2-methyltetrahydrofuran by bromine gives the dibromide, 99. The primary halide is sufficiently less hindered so that reaction with potassium phthalimide affords exclusively the product of displacement of that halogen (100). Alkylation of the aminoquinoline with lOO affords the secondary amine, 101. Removal of the phthalimide group by means of hydrazine yields primaquine (102). ... 

Some of the initial enthusiasm surrounding chiral SFC was tempered by the fact that many of the same separations had already been achieved by LC [29]. Therefore, researchers were reluctant to add SFC to their analytical laboratories. In some instances, SFC does yield separations that can not be achieved on the same CSP in LC [30, 31]. The enantioseparation of primaquine, an antimalarial compound, on a Chiralcel OD CSP is illustrated in Fig. 12-1 [32]. This compound was not resolved on the same CSP in LC [33]. The reverse situation, where a separation obtained in LC may not be observed on the same CSP in SFC, can also occur [34]. These disparities seem to be related to differences in analyte-eluent and eluent-CSP interac-... 

Favism is the haemolysis obseived after eating Vica fava. This reaction is observed in individuals with glucose-6-phosphate dehydrogenase deficiency. This common deficiency is also responsible for haemolysis in response to the antimalarial drug primaquine and others. 

Ahmad and Shukla [11] determined primaquine and other antimalarial aminoqui-nolines by vanadium titration. The drugs were determined by oxidation with aqueous ammonium vanadate solution and back titration of the unconsumed reagent with aqueous acidic ammonium ferrous sulfate with V-phenyl anthranilic acid indicator. 

Abdel-Salam et al. [21] described a sensitive and simple spectrophotometric method for the determination of primaquine and other antimalarial drugs. The method is based on the formation of complexes between iodine (as an acceptor) and the basic drug in chloroform solution. Optimum conditions were established for the determination of primaquine, in pure form or in pharmaceutical preparation. Results were accurate and precise. 

Gu et al. [27] used a spectrofluorimetric method for the determination of the long-acting antimalarial primaquine octanoate. 

Ibrahim et al. [30] described a fluorimetric method for the determination primaquine and two other aminoquinoline antimalarial drugs using eosin. Powdered tablets or ampule contents containing the equivalent of 50 mg of the drug was extracted with or dissolved in water (100 mL). A 10 mL aliquot was mixed with 10 mL of aqueous ammonia, 1 mL of 0.001% eosin (C.I. acid red 87) in dichloro-ethane, and dichloroethane was added to volume. Primaquine was determined fluorimetrically at 450 nm (excitation at 368 nm). Calibration graphs were rectilinear for 0.1-5 pg/mL of primaquine. Recoveries were quantitative. The method could be readily adapted for determination of the drug in biological fluids. 

Cheng et al. reported the use of a synchronous fluorimetric method for the determination of primaquine in two-component antimalarial tablets [31]. Ground tablets were dissolved in water and the mixture was filtered. The fluorescence intensities of chloroquine phosphate and primaquine phosphate, in the filtrate, were measured at 380 nm (excitation at 355 nm) and 505 nm (excitation at 480 nm), respectively. The calibration graphs were linear from 1 to 8 pg/mL of chloroquine phosphate and 10 to 110 pg/mL of primaquine phosphate. The mean recoveries were 98.2-101.49% and the relative standard deviations were 2.23%. 

Issa et al. [34] used 2,3-dichloro-5,6-dicyano-p-benzoquinone for the spectropho-tometric determination of primaquine and other antimalarials. The drugs were determined in tablets by a spectrophotometric method based on the reaction with 2.3-d ich loro-5.6-dicyano-p-benzoquinone and measurement of the absorbance at 460 nm. The reaction occurred fastest in methanol and acetonitrile to yield a radical anion, which was detected by electron spin resonance. The color attained its maximum intensity after 5 min and remained stable for at least 1 h. The absorbance versus concentration curve obeyed Beer s law in the concentration range 1-4 mg per 100 mL. The recovery was 99.9-102.6%. 

El-Ashry et al. [36] studied the complex formation between the bromophenol blue, primaquine, and other important aminoquinoline antimalarials. The colorimetric method used was described as simple and rapid and is based on the interaction of the drug base with bromophenol blue to give a stable ion-pair complex. The spectra of the complex show maxima at 415 420 nm with high apparent molar absorptivities. Beer s law was obeyed in the concentration range 1-8,2-10, and 2-12 pg/mL for amodiaquine hydrochloride, primaquine phosphate, and chloroquine phosphate, respectively. The method was applied to the determination of these drugs in certain formulations and the results were favorably comparable to the official methods. 

Sastry et al. [41] used a new spectrophotometric method for the estimation of primaquine, using 3-methylbenzothiazolin-2-one hydrazone. An aqueous extract of the sample of powdered tablets (containing 50 pg/mL of primaquine phosphate was mixed with 1 mL each of aqueous 8.5 mM 3-methylbenzothiazolin-2-one hydrazone and 11.84 mM CelV (in 0.72 M sulfuric acid), the mixture was diluted to 10 mL, and the absorbance was measured at 510 nm versus a reagent blank. Beer s law was obeyed for 0.7-12 pg/mL of the drug and for 50 pg, the coefficient of variation was 0.52%i (n = 8). Other antimalarials and pharmaceutical adjuvants did not interfere. 

Sastry et al. [42] reported the use of an extractive spectrophotometric method for the determination of primaquine and other antimalarial agents using Fast Green FCF (C.I. Food Green 3) or Orange II (C.I. Acid Orange 7). Sample solution... 

Mahrous et al. [43] determined primaquine and other antimalarials by use of chloranilic acid for the colorimetry. Primaquine was treated with 0.2 chloranilic acid solution in acetonitrile to give a purple solution with absorption maximum at 522 nm. Beer s law was obeyed from 0.04 to 0.2 mg/mL. Analysis of pharmaceutical formulation by this method is as accurate as the official method. 

Ibrahim et al. [49] described a spectrophotometric method for the determination of primaquine and other antimalarial agents in pharmaceuticals. Powdered tablet or ampule contents containing 25 mg of primaquine phosphate, was dissolved in water and the solution was made alkaline with 6 M ammonia before extraction with chloroform. The extract was evaporated to dryness and the residue was dissolved in acetonitrile. A portion of the solution was mixed with 0.04% tetracyanoethylene solution in acetonitrile and diluted to volume with acetonitrile. After 10 min, the absorbance was measured at 415 nm for primaquine. Beer s law was obeyed from 2 to 12 mg/mL. The results agreed well with those of the United State Pharmacopoeia XX method. 

El-Brashy [51] reported the determination of primaquine and other antimalarials via charge-transfer complexes. Powdered sample of primaquine phosphate was dissolved in water and the solution was adjusted to an alkaline pH with 6 M ammonia and extracted with chloroform. The extract was dried with anhydrous sodium sulfate, filtered, and evaporated to dryness under nitrogen and the residue was dissolved in acetonitrile. Portions of the solution were mixed with 0.2% 7,7,8,8-tetracyanoquinodimethane, diluted with acetonitrile, and set aside for 10 min before the absorbance was measured at 845 nm versus a reagent blank. The calibration graphs were linear from 0.4 to 3 pg/mL and recovery was 98%. 

Hassan et al [65] used a method for the determination of primaquine and other antimalarials, through ternary complex formation. The analytical aspects of the reaction between the widely used antimalarial drugs with cobalt and thiocyanate to form ternary complexes are described. Alternatively, determination of the cobalt content of the nitrobenzene extract using atomic absorption spectroscopy provided an indirect method for the determination of the drugs. Both methods are applied to the analysis of pharmaceutical preparation and the results obtained agreed well with those obtained with official methods. 

Dwivedi et al. used a thin-layer chromatographic densitometric and ultraviolet spectrophotometric methods for the simultaneous determination of primaquine and a new antimalarial agent, CDRI compound number 80/53 [68]. The new antimalari-al agent, compound 80/53 is unstable in acidic conditions where it is converted into primaquine. To conduct stability studies of this compound, thin-layer chromatography densitometric and ultraviolet spectrophotometric determination methods were developed. These methods are also suitable of the determination of compound 80/53 or primaquine in bulk and pharmaceutical dosage forms. 

Phinney et al. [Ill] investigated the application of citrus pectins, as chiral selectors, to enantiomer separations in capillary electrophoresis. Successful enantioreso-lution of primaquine and other antimalarials, was achieved by utilizing potassium polypectate as the chiral selector. Changes in pH, chiral additive concentration, and capillary type were studied in relation to chiral resolution. The effect of degree of esterification of pectin materials on chiral recognition was evaluated. 

Moore and Hemmens [119] studied the photosensitization of primaquine and other antimalarial agents. The drugs were tested for in vitro photosensitizing capability by irradiation with 365 nm ultraviolet light in aqueous solutions. The ability of these compounds to photosensitize the oxidation of 2,5-dimethylfuran, histidine, trypotophan, or xanthine, and to initiate the free radical polymerization of acrylamide was examined in the pH range 2 12. Primaquine does not have significant photochemical activity in aqueous solution. 

Bangchang et al. [142] studied a number of antimalarial drugs for their effect on the metabolism of primaquine by human liver microsomes (N = 4) in vitro. The only metabolite generated was identified as carboxyprimaquine by cochromatography with the authentic standard. 

Bergqvist and Churchill [146] reviewed the methods used for the detection and determination of primaquine and other antimalarial drugs and their metabolites in body fluids. 

Olenick [152] presented a review on primaquine. Fernex and Leimer [153] reviewed the pharmacology and clinical properties of primaquine and other antimalarial agents. 

As hydroxyl or hydroxyl-like radicals are produced by the superoxide-driven Fenton reaction, superoxide overproduction must also occur in thalassemic cells. First, it has been shown by Grinberg et al. [382], who demonstrated that thalassemic erythrocytes produced the enhanced amount of superoxide in comparison with normal cells in the presence of prooxidant antimalarial drug primaquine. Later on, it has been found that the production of superoxide and free radical-mediated damage (measured through the MetHb/Hb ratio) was much higher in thalassemic erythrocytes even in the absence of prooxidants, although quinones (menadione, l,4-naphthoquinone-2-methyl-3-sulfonate) and primaquine further increased oxidative stress [383]. Overproduction of superoxide was also observed in thalassemic leukocytes [384]. 

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