Pseudoephedrine hydrochloride

We proposed using MLC for assay of azithromycin in tablets and capsules. As alternative conventional reversed-phase HPLC method MLC was used for analysis of Biseptol (sulfamethoxazole and trimethoprim) tablets and injection. The MLC was proposed to assay of triprolydine hydrochloride and pseudoephedrine hydrochloride in tablets as alternative normal-phase HPLC method described in USP phamiacopoeia. 

Actifed is a medicinal preparation in which the effective components are the two drugs pseudoephedrine hydrochloride and triprolidine hydrochloride. The absorption spectrum of Actifed tablets dissolved in 0.1M hydrochloric acid is similar to that shown in Fig. 17.14(a) which is clearly of no value for quantitative determinations. A second derivative spectrum however is similar in character to that shown in Fig. 17.14(6) in which peak C corresponds to the pseudoephedrine hydrochloride and D to the triprolidine hydrochloride and from which it is possible to make quantitative measurements. Experience showed that it is advisable to use different response times for the two peaks with the instrument used a response setting of 3 was found to give the best results for pseudoephedrine hydrochloride, whilst a setting of 4 was best for the triprolidine hydrochloride. 

Procedure. Prepare standard solutions of pseudoephedrine hydrochloride by weighing out accurately about 60 mg into a 500 mL graduated flask. Add about 50 mL 0.1M hydrochloric acid to dissolve the solid and then make up to the mark with 0.1 M hydrochloric acid. In a series of 50 mL graduated flasks place... 

Pseudoephedrine hydrochloride occurs as fine white to off-white crystals or as a powder having a faint odor1... 

The infrared spectrum of pseudoephedrine hydrochloride is shown in Figure 1. It was obtained as a 0.2% dispersion of pseudoephedrine hydrochloride in KBr with a Nicolet Model 7199 FT-IR spectrophotometer.2 Table I gives the infrared assignments consistent with the structure of pseudoephedrine hydrochloride. 

The ultraviolet spectrum of pseudoephedrine hydrochloride in ethanol was obtained with a Beckman ACTA CIII ultraviolet spectrophotometer and is shown in Figure 3.4 Pseudoephedrine hydrochloride exhibits absorption maxima at 208, 251, 257, and 264 nm with extinction coefficients of 8300, 161, 201, and 161, respectively. 

The low resolution mass spectrum of pseudoephedrine hydrochloride is shown in Figure 4.5 It was obtained with a Varian MAT CH5-DF mass spectrometer. Direct probe at 80°C into the ion source was used to obtain the mass spectrum. 

Solubility of Pseudoephedrine Hydrochloride at 25°C Solvent Water Chloroform Ethanol Ether... 

The DSC curve of pseudoephedrine hydrochloride obtained with a Perkin Elmer DSC-1B differential scanning calorimeter is shown in Figure 5.7 The heating rate was 5°C/min. The heat of fusion is 6.4 Kcal/mol. The melting point (uncorrected) is 184°C. 

The crystal properties of pseudoephedrine hydrochloride were determined with a GE model XRD-6 x-ray diffractometer using Zr filtered MoK radiation on a crystal grown from water.8 Pseudoephedrine hydrochloride has an orthorhombic crystal system belonging to the P212121 space group. The cell dimensions are a=25.358 A, b=6.428 A, c=6.901 A with each cell containing four molecules. 

Pseudoephedrine hydrochloride is prepared by a Welsh rearrangement10 of -ephedrine hydrochloride with acetic anhydride followed by deacetylation with hydrochloric acid.11 -Ephedrine can be resolved from d -ephedrine with -mandelic acid.12 -Ephedrine occurs naturally in certain plants of the Ma Huang species. 

Pseudoephedrine hydrochloride can be considered a stable compound in bulk and in formulations. After 4-weeks under fluorescent lights (2400 ft. candles) and ultraviolet light (190 pw/cm2) no discoloration or chemical degradation was observed. The bulk drug was stable for at least 6 months at 37°C and 3 months at 50°C. Tablet and syrup formulations stored at 15-30°C for 5 years showed no appreciable degradation. 13... 

The major biotransformations of pseudoephedrine hydrochloride are parahydroxylation, N-demethylation, and oxidative deamination.14 The proposed pathways for the metabolism of pseudoephedrine are shown in Figure 6. 

In a study with human subjects, whose urine pH was controlled with sodium bicarbonate and ammonium chloride, it was found that 10-25% of the administered pseudoephedrine hydrochloride was metabolized to norpseudoephedrine and the elimination of pseudoephedrine and norpseudoephedrine was related to urine pH. As the urine pH increased, the serum half-life of pseudoephedrine and norpseudoephedrine increased.15 In another similar study it was found that a decrease... 

The results of the elemental analysis of pseudoephedrine hydrochloride are given in Table IV.6 The analysis was performed on a NF Reference Standard. 

Pseudoephedrine hydrochloride is dissolved in a mixture of glacial acetic acid and mercuric acetate test solution. A standardized solution of 0.1N perchloric acid is used to titrate the solution to a blue-green end point with crystal violet indicator. Each ml of 0.1N perchloric acid is equivalent to 0.1 mmole of pseudoephedrine hydrochloride.1... 

An ultraviolet spectrophotometric analysis is used to assay pseudoephedrine hydrochloride in tablets. A portion of finely powdered tablets equivalent to approximately 30 mg of pseudoephedrine hydrochloride is placed in a distilling flask which is part of a micro-steam distillation apparatus. Sodium chloride, water, and concentrated sodium hydroxide are added. A minimum of 30 ml of distillate is collected in a volumetric flask containing dilute hydrochloric acid. The flask is made to volume with distilled water and the absorbance of the solution is determined at 257 nm in 1 cm cells and compared to a solution of known concentration of NF Pseudoephedrine Hydrochloride Reference Standard.1... 

An ultraviolet spectrophotometric method based on the absorbance of a periodate oxidation product of pseudoephedrine hydrochloride will be the official method of analysis in the USP XX.19,20 A portion of tablets or syrup in water is placed in a separatory funnel. Sodium bicarbonate and sodium metaperiodate are added. After standing for 15 minutes, 1 N HC1 is added. The solution is extracted with hexane. The hexane extract is filtered and its absorbance determined at 242 nm in 1 cm cells. The amount of the oxidation product of pseudoephedrine hydrochloride is determined by comparison of the sample absorbance against the absorbance of a Pseudoephedrine Hydrochloride Reference Standard treated in the same manner. 

Pseudoephedrine hydrochloride in syrup formulations has been analyzed by colorimetry. Pseudoephedrine forms a stable blue-colored chelate with cupric sulfate at pH 12.5. The complex has a maximum absorbance at 500 nm. The complex is extracted from an aqueous layer with 1-pentanol. Interfering substances such as glycerine and sugars normally found in syrup formulations, which form complexes with cupric sulfate, are not extracted into 1-pentanol.21... 

High performance liquid chromatography has been used to analyze pseudoephedrine hydrochloride and dosage forms containing pseudoephedrine hydrochloride. Table V gives the HPLC conditions used for separations. 

Table VI lists the various TLC systems used for pseudoephedrine hydrochloride.

TLC Systems for Pseudoephedrine Hydrochloride Mobile Phase Adsorbent Rf Reference... 

Paper chromatography has been used to separate and detect pseudoephedrine hydrochloride from other pharmacologically active amines. Whatman No. 1 paper developed in n-butanol water 95% acetic acid (4 5 1), n-butanol toluene water 95% acetic acid (10 10 5 5), ethyl acetate water 95% acetic acid (3 3 1), or chloroform water 95% acetic acid (10 5 4) gave Rf values of 0.73, 0.35, 0.57, and 0.52 for pseudoephedrine hydrochloride respectively. Visualization of pseudoephedrine hydrochloride was done by spraying the chromatogram with 0.5% bromcresol green in methanol or 0.2% nin-hydrin in acetic acid butanol 5 95.30... 

Pseudoephedrine hydrochloride has been separated from other amines by gas chromatography. The oxazolidine... 

An on-column acetic anhydride derivatization technique has been described for pseudoephedrine hydrochloride. Immediately after injection of a solution of pseudoephedrine onto a 20% SE-30, 1.8 m x 7 mm i.d. glass column at 125°C, an injection of acetic anhydride was made. The pseudoephedrine derivative formed on column has a retention time of 55.5 minutes as compared to a retention time of 8.7 minutes for underivatized pseudoephedrine.34... 

A variety of methods have been used to determine pseudoephedrine hydrochloride levels in plasma and urine by gas chromatography. Bye and co-workers3s extracted basefied plasma or urine with diethyl ether. The ether extract concentrate was chromatographed on a 1.2 m x 2mm i.d. glass column packed with 2% Carbowax 20 M +5% KOH. The column was maintained at 187°C for plasma samples and 150°C for urine samples. 

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