Pseudoephedrine hydrochloride, extraction

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... 

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. 

Eckard and Taylor reported the modifier and additive effects on the SFE of pseudoephedrine hydrochloride from Suphedrine tablets, achieving a recovery of 82% (142). Also, racemic ephedrine was resolved using supercritical CO2 (143). The temperatures for crystallization were 35-75°C and the pressures were 100-350 bar. The samples were analyzed using electrophoresis. The experimental error for the resolution was 0.3 mol%. Regarding the extraction of isomers, 13-cf5-retinoic acid and its photoisomers were extracted from pharmaceutical formulations, with CO2 modified with 5% methanol at 45°C and 329 bar (144) static and dynamic extraction times of 2.5 and 5 min, respectively, were used. The extracts were analyzed by FIPLC. The recovery of 13-cA-retinoic acid from spiked placebo forms was 98.9%, 98.9%, 98.8%, and 100% for cream, gel, capsule, and beadlet, respectively, with RSDs (four replicates) ranging from 0.6% to 0.9% its photoisomers were also extracted, with recoveries of 90.4-92.4% with RSDs (four replicates) of 1.5-3.4%. 

Opium alkaloids such as codeine, thebaine, papaverine, and noscapine exhibit high solubility (0.09-0.9 mg/g) in supercritical fluids including CO N,0, CHF, [37]. However, in spite of their high solubilities, they were not extracted from plant material by pure CO, to the degree expected [29], possibly because these alkaloids exist as their salt forms in plant tissue. In this chapter, the examples that show the difference of the solubilities between alkaloidal free bases and salts are presented. For this comparison, the solubilities of the free bases of hyoscyamine (1), scopolamine (2), pseudoephedrine (6) were measured and compared with those of their hydrochloride salts (Figures 3 and 4). 

Although there were some differences on the effects of temperature and pressure according to each particular compound, the free bases of hyoscyamine (1), scopolamine (2), and pseudoephedrine (6) were all found to be highly soluble in supercritical CO,. However, the hydrochloride salts of these compounds were scarcely extracted by pure CO, under any conditions employed. These results were consistent with preliminary evidence indicating that these alkaloids are not extracted from plant materials by pure CO,. This means that the alkaloids in living cells in the plant are not in the form of their free bases but rather as water-soluble salts in the cell vacuole [40]. Therefore, it was necessary to develop a procedure to enhance the solubilities of alkaloidal salts in CO,. 

Considering the chemical characteristics, ephedrine has two chiral centers, and therefore four isomers can be identified ( )-ephedrine and ( )-pseudoephedrine [39]. (lR,2S)-(—)-ephedrine is the major isomer found in Ephedra sp., and pharmacological studies have shown it as responsible for the pharmacological activities of ephedra. Not only (—)-ephedrine has the widespread use but also (+)-pseudoephedrine is added in over-the-counter decongestant preparations [40]. The four isomers of ephedrine may be naturally present in Ephedra species, and they are usually used as a hydrochloride form, being the classical purification method for ephedrine hydrochloride a combination of conventional infusion and organic solvent extraction or adsorption [41]. Other alkaloids are also present in smaller amounts, and the minor ephedrine alkaloids include (+)-pseudoephedrine and the demethyl analogues (—)-norephedrine and (+)-norpseudoephedrine [40]. 

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