Amodiaquine hydrochloride

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. 

Hassan et al [18] used a spectrophotometric method for the simultaneous determination of primaquine with amodiaquine mixtures in dosage forms. Crushed tablets containing primaquine phosphate and amodiaquine hydrochloride were extracted with 0.1 M hydrochloric acid, and the mixture was filtered. A portion of the filtrate was diluted with 0.1 M hydrochloric acid, and the absorbance of this solution was measured at 282 and 342 nm against hydrochloric acid. 

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. 

Materials Required Amodiaquine hydrochloride 0.3 g dilute ammonia solution (42.5 ml of strong ammonia solution to 100 ml in water) NO. 4 sintered glass crucible. 

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. 

Chloramphenicol Sodium 464.8 Amodiaquine Hydrochloride 488.0 Chloropyrilene Citrate... 

Ammonia buffer (pH9.5), 1169 Ammonia solution, dilute, 1169 Ammonia solution, strong, 1169 Ammoniacal Silver Nitrate (test), 129 Ammonium mandelate, 718 Ammonium polysulphide solution, 1169 Ammonium sulphide solution, 1169 Amobarbital, 353 Amobarbital sodium, 353 Amodiachin, 347 Amodiaquine, 347 Amodiaquine hydrochloride, 347 Amolanone, xvii Amopyroquine, xvii Amorphan Depot, 437 Amosyt, 549... 

Chloroquine and other aminoquinolines are used in the prophylaxis or therapy of malaria and other parasitic diseases. Chloroquine and hydroxychloroquine are also used in the treatment of rheumatoid arthritis. Drugs in this class include chloroquine phosphate (Aralen ), amodiaquine hydrochloride (Camoquin ), hydroxychloroquine sulfate (Plaquenil ), mefloquine (Lariam" ), primaquine phosphate, and quinacrine hydrochloride (Atabrine ). Chloroquine overdose is common, especially in countries where malaria is prevalent, and the mortality rate is 10-30%. Quinine toxicity is described on p 326. 

Amodiaquine hydrochloride is 4-(7-chloro-4-quinolylamino)-2-(diethylaminomethyl) phenol dihydrochloride dihydrate (4). 

Official monographs for amodiaquine hydrochloride are given in Argentinian (1966), British (1988), Brazilian (1977), Egyptian (1984), French (1982), Indian (1985), International (1981) and United States (1990) Pharmacopeias. 

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. 

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