Primaquine phosphate

Phosphate Primaquine phosphate, Primaquine (diphosphate de), Primaquini diphosphas, Primaquinbisdihydrogenphosphat, Primaquine diphosphate, Difosfato de Primaquina, Primachina Fosfato, Primaquinum Phosphoricum SN-13272 [1-6],... 

Primaquine phosphate contains not less than 98.5% and not more than the equivalent of 101.5% of (i Y)-8-(4-amino-l-methylbutylamino)-6-methoxyquinoline diphosphate, calculated with reference to the dried substance. 

Test 1 Dissolve 15 mg of primaquine phosphate in 0.01 M hydrochloric acid and dilute to 100 mL with the same acid. Examined between 310 and 450 nm, according to the general procedure (2.2.25), the solution shows two absorption maxima, at 332... 

Dissolve 0.2 g of primaquine phosphate in 40 mL of anhydrous acetic acid R, heating gently. Titrate with 0.1 M perchloric acid determining the endpoint... 

Primaquine phosphate contains not less than 98% and not more than 102% of C15H21N3O 2H3PO4 calculated on the dried basis. 

Test 1 Infrared absorption. This test must be carried out according to the general procedure <197K>. The spectrum obtained from the sample of primaquine phosphate should be identical with that spectrum obtained from USP Primaquine Phosphate RS. 

Test 2 The residue obtained by ignition of primaquine phosphate responds to the test for pyrophosphate as described under phosphate, the test must be carried out as described in the general procedure <191 >. 

Loss on drying. By following the general procedure <731>, dry primaquine phosphate at 105 °C for 2 h. It loses not more than 1% of its weight. 

Dissolve about 700 mg of primaquine phosphate, accurately weighed, in about 75 mL of water in a beaker, add 10 mL of hydrochloric acid, and proceed as directed under Nitrite Titration in the general procedure <451 >, beginning with cool to about 15°C . Each milliliter of 0.1 M sodium nitrite is equivalent to 45.53 mg of C15H21N3O2H3PO4. 

Primaquine phosphate tablets contain not less than 93% and not more than 107% of the labeled amount of C15H21N3O2H3PO4. 

Digest a quantity of finely powdered tablets, equivalent to about 25 mg of primaquine phosphate, with 10 mL of water for 15 min, and filter. 

Procedure Separately inject into the chromatograph equal volumes (about 20 pL) of the solution under the test and a Standard solution having a known concentration of USP primaquine phosphate RS in the same Medium and record the chromto-grams. Measure the responses for the major peak, and calculate the amount of C15H21N3O2H3PO4 dissolved. 

Weigh and finely powder not less than 30 tablets. Weigh accurately a portion of the powder, equivalent to about 700 mg of primaquine phosphate, and transfer to a... 

Test 2 Mandelin s Test Dissolve 0.5 g of ammonium vanadate in 1.5 mL of water and dilute to 100 mL with sulfuric acid. Filter the solution through glass wool. Add a drop of the reagent to the primaquine phosphate sample on a white tile. A orange — violet color is produced [2]. 

Papovic et al. [14] used a conductometric method for the determination of primaquine phosphate. This method is recommended with perchloric acid, silicotungstic acid, and sodium hydroxide as titrants. Conductometric curves obtained with... 

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. 

Vishwavidyalaya et al. [22] used a difference-spectrophotometric method for the estimation of primaquine phosphate in tablets. One portion of powdered tablets, equivalent to 7.5 mg of primaquine phosphate, was extracted with hydrochloric acid-potassium chloride buffer (pH 2) and a second portion was extracted with phosphate buffer (pH 10). Primaquine phosphate was determined from the difference in absorbance of the acid and alkaline extracts at 254.2 nm. The calibration graph was rectilinear from 2 to 14 pg/mL of primaquine phosphate. Recovery was 98.6% and no interference was observed from excipients. Results compared with those by the British Pharmacopoeial method. 

Min et al. [23] determined primaquine phosphate, in tablets, by an ultraviolet spectrophotometric method. Sample was treated with 0.01 M hydrochloric acid and the resulting solution (500 pg/mL) was diluted to 50 mL with 0.01 M hydrochloric acid. The absorbance of the solution was measured at 265 nm versus a reagent blank. Beer s law was obeyed from 8 to 20 pg/mL of primaquine phosphate. Recovery was 100.2% (n = 5) and the coefficient of variation was 0.5%. Results were consistent with those obtained by a pharmacopoeial method. 

Talwar et al. [26] described a difference spectrophotometric method for the estimation of primaquine phosphate in tablets. The method is based on the... 

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%. 

Rao and Rao [33] used a rapid, sensitive, and simple colorimetric method for the estimation of primaquine phosphate. The method is based on its reaction with sodium vandate to give a pink color, which has an absorbance maximum at 550 nm. Beer s law is obeyed for 2-30 pg/mL. 

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. 

John et al. [37] described a colorimetric method for the estimation of primaquine phosphate. Sample solutions of different dilutions (0.15-0.6 mL) of the drug (6-24 pg/mL) were treated with 5 mL of 1% cerric ammonium sulfate in dilute nitric acid and made up to 25 mL with water. The absorbance of the resulting light purple solution was measured at 480 nm after similar 30 min. Beer s law was obeyed from 5 30 pg/mL of primaquine phosphate. The method is applicable to bulk formulations in addition to tablets and capsule formulation. 

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. 

Rao et al. [45] determined primaquine phosphate, in pharmaceutical dosage forms, by using a colorimetric method. Powdered tablets containing the equivalent of 100 mg of primaquine phosphate were heated with 25 mL of water for 10 min, the solution was cooled and filtered, and 10 mL portion of the filtrate was diluted 10-fold with water. A 5-mL portion of this solution was mixed with 5 mL of pH 5 buffer solution, 1 mL of 0.08%. amidopyrine solution in aqueous 95% alcohol and 2 mL of aqueous 0.1% sodium periodate. After 10 min, 0.5 mL of aqueous sodium metabisulfite solution was added and the absorbance was measured at 580 nm. Beer s law was obeyed between 4 and 43 pg/mL of primaquine phosphate. Recoveries were quantitative. 

Rao et al. [46] reported the use of a spectrophotometric method for the determination of primaquine phosphate with ninhydrin. Standard solution of 0.01% primaquine phosphate solution (3 mL) or solution prepared from the drug or its tablets was mixed with 2 mL of water, 5 mL of 2-methoxyethanol and then with 4 mL of ninhydrin reagent. The mixture was boiled for 35 min, and, after cooling and dilution to 25 mL with water, the absorbance was measured at 570 nm versus a reagent blank. Beer s law was obeyed from 4 to 20 pg/mL with recoveries of 99.4— 100.2% for 25 mg of primaquine phosphate. 

El-Kommos and Emara [47] determined primaquine and other secondary aromatic amines pharmaceuticals by a spectrophotometric method using 4-dimethyl amino cinnamaldehyde. The reaction of the reagent with primaquine and with the other amines was investigated. Powdered tablets were extracted with methanolic 0.1 M perchloric acid. The extract was mixed 1 1 with methanolic 0.2% of 4-dimethyl amino cinnamaldehyde and the mixture was diluted with methanol before measurement of the absorbance at 670 nm for primaquine phosphate. Beer s law was obeyed for 2-20 pg/mL of primaquine. The pink and green color formed with primaquine was stable for at least 24 h. Recoveries were good. Amodiaquine did not interfere with the determination of primaquine. 

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. 

Sastry et al. [50] estimated primaquine in its tablet formulation. Powdered tablets equivalent to 100 mg of primaquine phosphate were dissolved in water, filtered, and filtrate was diluted to 100 mL with water. Portions of the solution were shaken with 3 mL of 5 mM brucine-0.16 M sulfuric acid, 1.5 mL of 5 mM sodium periodate and 2 mL of 1.2 M sulfuric acid and diluted to 9 mL with water. The solution was set aside for 20 min in a boiling water bath, cooled, and diluted to 10 mL with water. The absorbance was measured at 510 nm versus a reagent blank. Beer s law was obeyed from 20 to 140 pg/mL of primaquine phosphate. The coefficient of variation was 1.56% (n = 8). Recovery was 99.2%. 

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%. 

Berka et al [59] described an accurate and reproducible coulometric method, with chlorine electrogenerated at the anode, for the determination of micro quantities of primaquine phosphate. Titration was carried out in an anode compartment with a supporting electrolyte of 0.5 M sulfuric acid-0.2 M sodium chloride and methyl orange as indicator. One coulomb was equivalent to 1.18 mg of primaquine phosphate. The coefficients of variation for 0.02-0.5 mg of primaquine phosphate were 1-5%. Excipients did not interfere. 

Zhan [61] reported the use of an oscillopolarographic method for the determination of primaquine phosphate and other drugs in pure form and in pharmaceutical preparations. The sample solution was mixed with potassium bromide and 6 M hydrochloric acid and the mixture was titrated with 0.1 M sodium nitrite. A micro platinum electrode and a platinum electrode were used as indicators and reference electrodes, respectively. The mean recoveries were 96.88-99.88%. Results agreed well with those obtained by the Chinese Pharmacopoeia method. 

Katori et al [84] used a high performance liquid chromatographic method for the determination of primaquine phosphate tablets. Chromatography on a TSK Gel-4 (octadecylsilanized) column was used to determine the active ingredient in tablets and injections for treating tropical diseases. The mobile phase used is 26% acetonitrile in 0.05-M pH-3 phosphate buffer and the drug was detected at 260 nm. The peak area and peak height reproducibilities were <1.69%, and results compared well with those of other methods. 

Rao et al. [87] developed a high performance liquid chromatographic method for the determination of primaquine phosphate in pharmaceutical dosage form. A /(-Bondapak NH2 column with chloroform-methanol (60 40) as eluent was selected with sulfalene as internal standard. The method was convenient with recovery of approximately 100% for primaquine. 

Gaudette and Coatney [115] reported that primaquine phosphate was unstable when subjected to dry heat of 100 °C in the presence of sodium chloride for 24 h, when boiled in water for 24 h and when heated for 24 h at 100 or 200 °C in melted hydrogenated vegetable oil. These findings exclude the use of primaquine phosphate as a salt additive in cooking. Primaquine phosphate was isolated from the test preparations at alkaline pH by extraction into ethylene chloride, after which primaquine phosphate was returned to an aqueous phase by shaking with 0.1 N sulfuric acid the concentration of primaquine phosphate was then determined spectrophotometrically. The ultraviolet absorption curve of primaquine phosphate has maxima at 224, 266, 282, and 300 nm, and minima at 216, 250, 276, and 310 nm. A solution containing 10 yl/mL has an optical density of 0.375 at 282 nm optical densities were proportional to concentrations. 

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