Pseudoephedrine extractabilities

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. 

The heptafluorobutyric anhydride derivative of pseudoephedrine and electron capture detector have been used to enhance the sensitivity of the gas chromatographic method. Lin and co-workers36 and Cummins and Fourier37 extracted basefied urine or serum with benzene. Heptafluorobutyric anhydride is added to the benzene extract. The heptafluoro-ibutyric anhydride derivative extracted was chromatographed... 

A) UV spectrum of an extract elixir containing pseudoephedrine. dextromethorphan and triprolidine. (B) Second derivative spectrum of the extract. Note the absorbance maximum of dextromethorphan disappears. 

X 10 ml of chloroform. The chloroform layers are combined and evaporated to dryness using a rotary evaporator. The residue is dissolved in ca 10 ml of methanol and transferred to a 100 ml volumetric flask and then diluted to volume with mobile phase. The areas of the peaks obtained from the linctus extract are compared with a solution containing pseudoephedrine.HCl, dextromethorphan.HBr and triprolidine.HCl (structures shown in Fig. 11.14) at the same concentrations as would be expected in the linctus extract. 

The HPLC chromatogram of an extract from a linctus containing pseudoephedrine, dextromethorphan, triprolidine and methylparaben. ODS column 25 cm x 4.6 mm, mobile phase acetonitrile/0.05 M phosphate buffer pH 6.8 (35 65) 1 ml/min. UV monitoring at 260 nm. 

In addition to quenching excess hydride, the acidification and subsequent extraction steps remove pseudoephedrine and any tertiary amine reaction by-product the latter is otherwise difficult to remove by column chromatography. 

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,. 

Table 4. Yields of methylephedrine (ME), norephedrine (NE), ephedrine (E), and pseudoephedrine (PE) obtained by organic solvent extraction and SFE. Results are mg/g [41].u Reproduced with permission from Vieweg Publishing 1999.

Figure 11. Comparison of the gas chromatograms obtained by (A) 0.5 M H2S04 extraction and (B) SFE at 80 °C and 34.0 MPa using 20% diethylamine in methanol as a modifier. E = ephedrine (5), PE = pseudoephedrine (6) [41]. Reproduced with permission from Vieweg Publishing

Methylpentynol Bulk TLC extracted 50% EtOH (15 ml) RT, 30 min, centrifuged, filtered. ISTD-benzyltriethyl-ammonium chloride cm 75 ID, 28 kV Silica 0.005M barium hydroxide (pH 10) CHCI3-acctonc (4 1) KMnO, methylpseudo-ephedrine 5 min, pseudoephedrine 6.2 min, ephedrine 6.8 min, methylephedrine 7.8 min. norpseudoephedrine 8.1 min, norephedrine 8.8 min GC 2] [1]... 

Ephedrine is a component of the traditional Chinese remedy Ma Huang, extracted from Ephedra species, it is also used in nasal sprays as a decongestant. Pseudoephedrine is the active component of the decongestant Sudafed (so should that be Pseudephed ). 

Early in this chapter, we said that most of the molecules in nature are chiral, arid that Nature usually produces these molecules as single enantiomers. We ve talked about the amino acids, the sugars, ephedrine, pseudoephedrine, and tartaric acid—all compounds that can be isolated from natural sources as single enantiomers. On the other hand, in the lab, if we make chiral compounds from achiral starting materials, we are doomed to get racemic mixtures. So how do chemists ever isolate compounds as single enantiomers, other than by extracting them from natural sources We ll consider this question in much more detail in Chapter 45, but here we will look at the simplest way using nature s enantiomerically pure compounds to help us separate the components of a racemic mixture into its two enantiomers. This process is called resolution. 

Ichikawa M, UdayamaM, Imamura K, Shiraishi S, Matsuura M. HPLC determination of (+)-pseudoephedrine, (—)-ephedrine in Japanese herbal medicines containing ephedra herb using solid phase extraction. Chem Pharm Bull (Tokyo) 2003 51 635-639. 

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