Of amodiaquine hydrochloride

Chromatographic purity of amodiaquine hydrochloride can be examined on thin-layer plate coated with a 0.2S mm layer of silica gel G using solvent system chloroform (saturated with ammonium hydroxide) dehydrated alcohol (9 1). Under short-wavelength ultraviolet light, the chromatogram shows principal spot at about the same Rf value, and no secondary spot, as obtained with the USP Amodiaquine Hydrochloride RS (10). 

The ultraviolet spectra of amodiaquine and amodiaquine hydrochloride have been reported by Sunshine (12) and Clarke (7) respectively. The ultraviolet absorption characteristics are used for the identification of these drugs (4,10,13). The absorption spectrum of amodiaquine hydrochloride as a function of pH in the range 1-11.8 shows a hypsochromic effect at 343 nm, a hyperchromic effect at 305 nm and the isosbestic point at 323 nm (14). The effect of solvents and substitution on the ultraviolet spectra of amodiaquine has been studied and the changes of absorption bands E,K, and B discussed in detail (15). 

The ultraviolet spectrum of amodiaquine hydrochloride in 0.1 M hydrochloric acid was recorded on a Shimadzu 240 UV-Visible spectrophotometer and is shown in Figure 2. The uv spectral data reported for amodiaquine and amodiaquine hydrochloride are listed in Table 1. 

The infrared spectrum of amodiaquine has been determined in KBr disc (4). The principal peaks in the infrared spectrum of amodiaquine hydrochloride (KBr disc) are reported at 1565, 815, 1535, 1255, 869, 847 cm (7). Attenuated total reflectance infrared spectrum is used to detect amodiaquine hydrochloride in the solid state as a layer of crystals on adhesive tape. The method has been applied to the identification of the drug in tablet formulations. Common excipients such as starch, and... 

The infrared spectrum of amodiaquine hydrochloride as KBr disc was obtained with a Shimadzu IR 460 Infrared spectrophotometer and is shown in Figure 3. The assignments for characteristic bands are given in Table II. 

Figure 3. Infrared Spectrum of Amodiaquine Hydrochloride (KBr disc).

The H-NMR and C-NMR spectra of amodiaquine hydrochloride in DMSO-d6 were determined at 300 MHz and 75.4 MHz respectively on a Bruker AM-300 NMR spectrometer using tetramethylsilane as reference standard. The H-NMR determinations included spin decoupling experiments, 2D J-resolved and COSY-45 measurements (Figure 4-6). The C-NMR spectra comprised DEPT and hetero-nuclear (C-H correlation) measurements (Figure 7-9). The spectral assignments are listed in Table III. 

Figure 8. 75 MHz C-NMR Off Resonance Decoupled Spectrum of Amodiaquine Hydrochloride...

Hgure 9. Heteronucicar Chemical Shift Correlated (lleterocos ) 2D-NMK Spectrum of Amodiaquine Hydrochloride. 

The electron impact ionization spectrum of amodiaquine hydrochloride obtained at 70 eV using a solid probe insertion is shown in Figure 10. The spectrum was run on a Finnigan Mat 112S double focusing mass spectrometer coimected to a PDF 11/34 (DEC) computer system. It shows a molecular ion peak M at m/z 3S5. Since the molecule contains one chlorine atom, M+2 peak appears at m/z 357. Die proposed fragmentation pattern and prominent ions are given in Table IV. 

Dissolve 0.1 g of amodiaquine hydrochloride in 10 ml of water and add 2 ml of 2 M sodium hydroxide. Extract with two 20 ml quantities of chloroform, wash the combined chloroform extracts with 5 ml of water, dry with anhydrous sodium sulphate and evaporate to dryness. Dissolve the residue in 2 ml of chloroform. The infrared absorption spectrum of the resulting solution is concordant with the reference spectrum of amodiaquine. 

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... 

A method for the determination of amodiaquine hydrochloride in tablets by titration with N-bromosucdnimide has been developed (23). The sample is dissolved in water, treated with an acetic acid solution of the reagent and mixed vnth potassium iodide. The iodine released is titrated with sodium thiosulphate solution. The relative standard deviation for the titration is 2.12% and the recovery is 99.4 -101.0%. 

The determination of amodiaquine hydrochloride by oxidation with ammonium metavanadate solution and back titration of the unconsumed reagent with acidic iron (11) ammonium sulphate solution, using... 

N-phenylanthranilic add as indicator has been reported (24). The recovery of amodiaquine hydrochloride in the pure form and in pharmaceutical preparations is 99.83% (standard deviation 0.49%) and 99.69% (standard deviation 0.78%) respectively. The method is of general applicability and is quick and simple compared with the official methods. 

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 reacts with cobalt and thiocyanate to yield stable ternary complexes. These complexes are readily extractable in nitrobenzene to give a greenish-blue color with maximum absorption at 625 nm that can be used for quantitative determination. The mean recoveries for authentic samples of amodiaquine hydrochloride are 100.81 1.77% (p = 0.05). Alternatively, determination of the cobalt content of nitrobenzene extract by atomic absorption spectroscopy provides an indirect method for the determination of the drug with a mean recovery of 99.99 2.16%. Both the methods have been successfully applied to the assay of the drug in pharmaceutical preparations (30). 

The prolonged use of amodiaquine hydrochloride in the dosages necessary to treat lupus erythematosus and rheumatoid arthritis is not recommended, for corneal opacities and retinopathy, peripheral neuropathy, fatal blood (fyscrasias, and fatal hepatitis have been reported after these large dc ag (47). Patients have experienced involuntary movements, usually with speech difficulty, after large but not excessive doses of amodiaquine (48). It may cause birth defects if taken during pregnancy (49). 

The authors wish to thank the United States Pharmacopeial Convention, Inc., for donating a sample of amodiaquine hydrochloride. 

Both uncatalysed and RhCl3-catalysed oxidations of amodiaquine hydrochloride (AQ) with CAT have a negative fractional order in OH ions, whereas the catalysed reaction has a fractional order in the catalyst. The rates of Ir(III) catalysed chloramine-T oxidation of serine in acidic medium show a positive effect of substrate and H+ ion and a negative effect of Cr ion. ... 

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