Amodiaquine base

The underlying principle of the method is based upon the precipitation of amodiaquine base that is generated as a precipitate when the salt is decomposed in aqueous medium with dilute ammonia. 

The condensation of the nucleus and the side chain prepared above in (a) and (Z ) gives the amodiaquine base which on neutralization with hydrochloric acid yields the official compound. 

Amodiaquine base is extracted from urine into amyl acetate immediately after alkalinization. The addition of bromophenol blue in S% boric acid to the organic phase causes a green to blue coloring, depending on the concentration of the drug. The sensitivity of the test is 0.8 mg%. 

Amodiaquine, a Mannich base 4-aminoquinoline, eliminates blood stage parasites. Its mode of action is similar to that of chloroquine (see below) and there is some cross-resistance. 

Abou-Ouf et al. [16] described a spectrophotometric method for the determination of primaquine phosphate in pharmaceutical preparation. Two color reactions for the analysis of primaquine phosphate dosage form, which are based on 2,6-dichlor-oquinone chlorimide and l,2-naphthoquinone-4-sulfonate, were described. The reactions depend on the presence of active centers in the primaquine molecule. These are the hydrogen atoms at position 5 of the quinoline nucleus and the primary amino group of the side chain. The method was applied to tablets of primaquine phosphate and a combination of primaquine phosphate and amodiaquine hydrochloride. 

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. 

Theory Amodiaquine hydrochloride possesses two moles of inherent water of crystallization, and hence the precentage base is calculated with reference to the substance dried over P205 at a pressure not exceeding 5 mm of Hg. Usually, the assay is performed on one portion of the sample and the drying on a separate portion altogether. 

Amodiaquine is a Mannich base derivative related to chloroquine. While it is generally considered equivalent to chloroquine, more recent studies have shown that amodiaquine is superior to chloroquine in tackling resistant strains of Plasmodium falciparum, although there may be cross-resistance to chloroquine (SEDA-20, 260). 

The identification tests of amodiaquine hydrochloride based on comparison of infrared and ultraviolet absorption spectra, and reactions of chloride are reported in USP (10). 

The BP method (4) for the assay of amodiaquine hydrochloride as pure drug and in dosage forms is based on nonaqueous titration. A 0.2 g quantity of amodiaquine hydrochloride is dissolved in a suitable volume of anhydrous glacial acetic acid, 7 ml of mercury (11) acetate solution is added and the solution titrated with 0.1 M perchloric acid to a green end point using 1-naphtholbenzoin solution as indicator. In dosage forms, a... 

Amodiaquine can be determined in bulk and in dosage forms by a titrimetric method based on reaction with l,3-dibromo-5,5-dimethylhydantoin or N-bromosuccinimide as the titrant. The mixture is later treated with potassium iodide solution and the liberated iodine titrated with sodium thiosulphate solution. The recovery is about 100% (22). 

The USP assay (10) of amodiaquine hydrochloride in pure form and in tablets involves ultraviolet spectrophotometric determination. A quantity of the drug equivalent to about 300 mg is dissolved in dilute hydrochloric acid (1 100) to obtain a concentration of about IS The absorbance of this solution, along with a solution of undried USP Amodiaquine Hydrochloride RS in the same medium having a known concentration of about IS Ag/nil, is determined at 342 run using dilute hydrochloric add (1 100) as the blank. The quantity, in mg, of C20H22CIN3O, 2HQ in the portion of amodiaquine hydrochloride taken is calculated the formula 20c (Au/As), in which C is the concentration, in /Amodiaquine Hydrochloride RS in the standard solution and Au and As are the absorbances of the solution of amodiaquine hydrochloride and the standard solution respectively. The same method is applied to the assay of amodiaquine hydrochloride in tablets after extraction of the base into chloroform and then re-extraction with dilute hydrochloric acid (1 100). 

A simple, sensitive, and selective method for the determination of amodiaquine hydrochloride in tablets has been developed. It is based on a color reaction with chloramine-T in the pH range 7.4- 8.0. The chromogen is extracted with chloroform and the absorbance is measured at 442 nm. Beer s law is obeyed in the concentration range 1-200 n%/. The coefficient of variation has been found to be 0.64% and the recovery ranges between 100.3 and 102.5%. Chloroquine phosphate or primaquine phosphate do not interfere with the method (29). 

Amodiaquine hydrochloride tablets have been assayed by a method based on the reaction of the drug with 2,3-dichloro-5, 6-dicyano-p-benzoquinone and measurement of the absorbance at 460 nm. The color attains its maximum intensity after five minutes and remains stable for at least one hour. Beer s law is valid in the concentration range 1-4 mg/100 ml, and the recovery is 99.9-102.6% (32). Another colorimetric method for the determination of amodiaquine in tablets depends on its reaction with chloranilic acid in aqueous solution and measurement of the absorbance at 522 nm. The absorbance is linear over the concentration range 0.04 -0.20 mg/ml, and the recovery is 99.9-101.3% (33). 

A simple, rapid and sensitive method for the colorimetric determination of amodiaquine in bulk and in pharmaceutical preparations has been reported by Sastry et al. (34). It is based on the reaction of amodiaquine with potassium dichromate at pH 1.1 in the presence of sulphanilamide, and measurement of the absorbance of resulting solution at 510 nm. The color is stable for twenty-four hours. Beer s law is obeyed in the concentration range 20-120 relative standard deviation of the method is 0.94%, and the recovery is 99.0-101.0%. Chloroquine present even in ten-fold excess does not interfere with the determination. 

A highly sensitive method is based on the complexation of amodiaquine with ammonium molybdate. The bound molybdenum is converted into its thiocyanate, reduced, and the absorbance of the colored solution measured at 465 run. The Beer s law limits, molar absorptivity and Sandell s sensitivity for the amodiaquine complex are 50-300 g/25 ml, 1.75 X 10 cm and 0.026 tg/cm / 0.(K)1 absorbance unit, respectively. Recovery ranges from 98-101%. The color obtained is stable for twenty-four hours and common excipients do not interfere with the method (35). 

A column liquid chromatographic method for the simultaneous determination of chloroquine, amodiaquine and their monodesethyl metabolites in human plasma, red blood cells, whole blood and urine has been developed (41). The drugs and internal standards are extracted as bases with dichloromethane and then re-extracted into an acidic aqueous phase. Separation is achieved using a reversed-phase column and a mobile phase of phosphate buffer (pH 3.0) methyl cyanide (88 12). The absorbance of the drugs is monitored at 340 nm with a sensitivity limit of 10 pmol/ml. The mean overall recovery from each biological fluid is more than 75%. This method can be applied to therapeutic, pharmacokinetic, and epidemological studies. 

A series of artemisinin-based semisynthetic antimalarial derivatives, with all of them maintaining the key endoperoxide bridge, such as arteether (18), artemether (19), artesunate (20), and dihydroartemisinin (21), have been designed to improve the water solubility and the metabolic stability of artemisinin [53, 54], Among them, dihydroartemisinin (artenimol), is considered as a common active metaboUte of artemisinin derivatives [53, 54]. Currently, artemisinin-based therapies eombined with standard antimalarials such as amodiaquine, sulfadoxine-pyrimethamine, mefloquine, and lumefantrine are recommended by the World Health Organization (WHO) as first-line therapies for malaria [55, 56]. 

A prospective open-label, randomised trial comparing 14days of primaquine (0.25 mg base/kg) with either artensunate-amodiaquine or dihydroartemisinin-piperaquine (DHP) for the treatment of uncomplicated monoinfection with Plasmodium vivax malaria was performed Patients were randomised and given treatments without testing for G6PD status. Of the 331 patients, intravascular haemolysis occurred in 5 patients, of which 3 were males hemizygous for the G6PD-Mahidol mutation. Minor side effects were more frequent with artensunate-amodiaquine. 

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