Potentiometric and pHmetric Studies of Paracetamol

Acid-base titration of paracetamol in nonaqueous solvents was done. Procedure was followed for titration of paracetamol in different media like acetic acid, pyridine, dimethlformamide and ethyl alcohol with standard perchloric acid in glacial acetic acid, sodium ethoxide in ethyl alcohol using plantinum-calomel as well as glass-calomel electrode system. The equivalence point was located as accurately as possible by a differential graph of ∆E/∆V or ∆pH/∆V against V and concentration of test solution was computed. The acid-base titration of paracetamol is rapid and reproducible, and permits its determination in medicinal sample. The electrode systems vary with the solvent employed. The platinum-calomel electrode system is suitable where the solvent is glacial acetic acid in this case perchloric acid in glacial acetic acid is the titrant while the glass-calomel electrode system is suitable where the solvent is either pyridine, an alcohol or dimethyiformamide, the titrant consists of sodium ethoxide in ethyl alcohol.


Introduction
Paracetamol (acetaminophen) is one of the most popular analgesic and antipyretic drugs. Paracetamol is available in different dosage forms: tablet, capsules, drops, elixirs, suspensions and suppositories. Dosage forms of paracetamol and its combinations with other drugs have been listed in various pharmacopoeias [1,2]. The combination of paracetamol with dipyrone is used as an antipyretic, analgesic and anti-inflammatory drug. Numerous methods have been reported for the analysis of paracetamol and its combinations in pharmaceuticals or in biological fluids. Paracetamol has been determined in combination with other drugs using titrimetry [3,4], voltammetry [5], fluorimetry [6], colorimetry [6], UV-spectrophotometry [7][8][9], quantitative thin-layer chromatography (TLC) [10], high-performance liquid chromatography (HPLC) [11][12][13][14][15][16] and gas chromatography (GC) [17] in pharmaceutical preparations. Effect of electrophilic and electrodotic groups on the potentiometric titration of amides and other weak bases was studied [18]. Electrodotic groups enhance the potentiometric end point and electrophilic groups depress it, sometimes to the extent that the compound is not titratable. A combination of chloroform and acetic anhydride is a useful alternative medium for the titration of weak bases. A potentiometric method for determination of p-acetamidophenol was reported [19].
Analytical data are given for a representative number of amides, acetylated amines, and formylated amines [20]. In acetic acid, amides show little tendency toward salt formation with CH 3 COOH 2 + ; however, upon addition of acetic anhydride, additional acidic species become evident and measurable end points are observed [21].
An accurate, simple, reproducible and sensitive method for the determination of paracetamol, caffeine and dipyrone was developed and validated [26].
In present study acid-base titration of paracetamol in nonaqueous solvents was done. Procedure was followed for titration of paracetamol in different media like acetic acid, pyridine, dimethlformamide and ethyl alcohol with standard perchloric acid in glacial acetic acid, sodium ethoxide in ethyl alcohol using plantinum-calomel as well as glass-calomel electrode system. The equivalence point was located as accurately as possible by a differential graph of ∆E/∆V or ∆H/∆V against V and concentration of test solution was computed.

Methodology
All chemicals were of A.R. grade. Solvents were purified before use. Medicinal samples of paracetamol were collected from local market of different make. OSAW direct reading potentiometer was used to carry out redox titrations using bright platinum wire and saturated calomel electrodes. The pH-titrations were made with an ELICO LI-10 pH-meter in conjuction with Glass (EM-42) and calomel (ER-70) electrodes.
Acid-base titration of paracetamol in nonaqueous solvents was done by taking 0.2 g of Crocin paracetamol (Duphar) tablet in a 250 ml beaker and was dissolved in 25 ml of glacial acetic acid. A bright platinum wire electrode was dipped; the solution was connected to a calomel electrode via salt bridge and titrated with 0.1 N perchloric acid in acetic acid. Similar procedure was followed for titration of paracetamol in other media like pyridine, dimethlformamide and ethyl alcohol with standard sodium ethoxide in ethyl alcohol using plantinum-calomel as well as glass-calomel electrode system. The equivalence point was located as accurately as possible by a differential graph of ∆E/∆V or ∆H/∆V against V and concentration of test solution was computed.
addition of a titrant. Two types of potentiometric titrations, Oxidation-Reduction and Acid-Base titrations in nonaqueous solvents, have been performed, and interest is focused upon changes in the e.m.f. of an electrolytic cell as a titrant of precisely known concentration is added to a solution of the analyte namely paracetamol.
Acid-base titration data for paracetamol against perchloric acid and C 2 H 2 ONa in different media -glacial acetic acid, pyridine, dimethyl formamide and ethyl alcohol are shown in Table 1.

Results and Discussion
The results of estimation of paracetamol by potentiometric method are represented in Table 2. It is found that paracetamol can be easily titrated by potentiometric method in nonaqueous media like glacial acetic acid with perchloric acid and in pyridine, dimethylformamide and ethyl alcohol with sodium ethoxide. Good inflection point is obtained, results are reproducible and recovery is nearly 100%.

Acid-base reactions of paracetamol in nonaqueous solvents
Many acids or bases such as paracetamol that are too weak for determination in water become susceptible to titration in appropriate nonaqueous solvents. The major considerations in the choice of a solvent for acidimetric reactions are its acidity and basicity, its dielectric constant, and the physical solubility of a solute. Acidity is important because it determines to a large extent whether or not a weak acid can be titrated in the presence of a relatively high concentration of solvent molecules. Paracetamol, for example, cannot be titrated as an acid in aqueous solution because water is too acid and present in too high a concentration to permit the p-oxyacetanilide ion to be formed stoichiometrically by titration with a base. In other words the intrinsic basic strength of the p-oxyacetanilide ion and hydroxide ions are not sufficiently different for the reaction: In less acid solvents, such as dimethylformamide or pyridine, this titration can be carried out readily with a stronger basic titrant, the alkoxide ion:      Acidic properties of solvent such as acetic acid produce a pronounced levelling effect on the weak base (p-hydroxyacetanilide) and thus it gets converted into strong base which then can be titrated with strong acid. The titrant is a solution of perchloric acid in glacial acetic acid which has been standardized with potassium hydrogen phthalate. In an analogous fashion, basic solvents enhance the properties of weak acid (p-oxyacetanilide). It produce distinctive end point in dimethylformamide. The titrant is sodium ethoxide. The electrode systems vary with the solvent employed. The platinumcalomel electrode system is suitable where the solvent is glacial acetic acid in this case perchloric acid in glacial acetic acid is the titrant while the glass-calomel electrode system is suitable where the solvent is either pyridine, and alcohol or dimethylformamide, the titrant consists of sodium ethoxide. Acid-Base reaction involved in case of paracetamol while titrating with perchloric acid/sodium ethoxide can be represented as follows.

Conclusion
Based on potentiometric studies of paracetamol it is concluded that the acid-base titration of paracetamol is rapid and reproducible, and permits its determination in medicinal sample. The electrode systems vary with the solvent employed. The platinum-calomel electrode system is suitable where the solvent is glacial acetic acid in this case perchloric acid in glacial acetic acid is the titrant while the glass-calomel electrode system is suitable where the solvent is either pyridine, an alcohol or dimethyiformamide, the titrant consists of sodium ethoxide in ethyl alcohol. Weight of Tablet t g = aken Table 2: Analysis of crocin (duphar) paracetamol tablet by potentiometric acid -base titration methods.