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Codeine is an opioid analgesic used for the treatment of moderate to severe pain. It is recommended by the World Health Organization for relief of moderate cancer-related pain. However, excessive or habitual uptake can cause toxic symptoms (Bosch et al. 2007). Codeine (morphine 3-methyl ether) is also an opioid and has mild analgesic effect. It is often used in combination with other drugs such as aspirin and paracetamol in the treatment of mild to moderate pain. Because of its antitussive and constipating properties, it is also used in many cough and cold remedies (Williams, Hatch, and Howard 2001). A number of analytical methods for the determination of morphine and codeine in pharmaceutical preparations have been proposed, including high-performance liquid chromatography .However, the quality control of such drugs in pharmaceutical formulations demands simple, rapid, and low-cost analytical methods.

Codeine and Morphine are both amphiphilic compounds that are present in cationic form in acidic solution. Because such amphiphilic drugs can interact with surfactants (Schreier, Malheiros, and de Paula 2000; Kabir-ud-Din et al. 2008), analytical methodologies exploiting this property could be used for their determination. Aggregation of amphiphiles as a result of the electrostatic and hydrophobic interactions has been widely exploited in many pharmaceutical and analytical procedures. Recently, Fabios and coworkers (2003) have developed a new analytical methodology based on the capability of surfactants to form mixed aggregates with other amphiphilic molecules.



Shimadzu UV-120-02 and Cary-100 Varian UV-vis spectrophotometers were used to measure the absorbance and record the absorption spectrum, respectively. Titrations were performed in a 1.0-cm quartz cell by using a 1- to 10-µL Treff Lab micropipette. A Metrohm model 654 pH meter was used for pH measurements.

Solutions and Reagents

All reagents used were of analytical-reagent grade and were used as supplied. Doubly distilled water was used throughout. A 1-mM aqueous solution of NR was prepared by dissolving an appropriate amount of NR (Fluka) in 0.1 L of doubly distilled water with the aid of stirring. This solution was stable for at least 1 month. Stock solutions (10 mM) of the anionic surfactant, AOT, (Fluka) were also prepared in distilled water. The buffer solution used consisted of 0.25 M sodium acetate (Merck) with the pH adjusted to 3.5 with 1 M HCl. Stock solutions (200 mg L-1) of the cationic drugs, MH and CP, were prepared by dissolving suitable amounts of MH (Merck) and CP (Merck) in doubly distilled water.

General Procedure

Volumes of 1.0 mL of 1 mM NR solution, 2.5 mL of 0.25 M acetate buffer (pH 3.5), and appropriate volumes of standard drug solution to give a final concentration between 1 and 32 µg mL-1 (for MH) or 1 and 28 µg mL-1 (for CP) were placed in a 25-mL volumetric flask, and distilled water was added to the mark. Three mL of this solution were placed in a 1.0-cm quartz cell and titrated with 10 mM of AOT by means of a micropipette. After each addition of a small increment (1-2 µL) of the surfactant, absorbance was recorded at 532 nm. Titration curves were obtained by plotting the absorbance as a function of ...
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