Background

Acetaminophen (N-acetyl-p-aminophenol) is the active ingredient of Tylenol, a non-opiate, non-salicylate analgesic and antipyretic that occurs as a white, odorless, crystalline powder with a molecular formula of C₈H₉NO₂. Its formula weight is 151.16 [ref. 1].

Often recommended as a substitute for aspirin (acetylsalicylic acid), it provides temporary relief of minor aches and pain associated with heartburn, acid indigestion, flu and colds. Acetaminophen acts by elevating the pain threshold and antipyresis through action on the hypothalamic heat regulation center. Readily absorbed and distributed throughout fluids in the body, unchanged acetaminophen is excreted in the urine. Products metabolized through the liver appear in the urine within 24 hours [ref. 2]. Unlike opioid analgesics, APAP does not cause euphoria or alter moods in any way, and is completely free of addiction and withdrawal. It went on sale in 1955 as Tylenol. A historical background and discussion of its pharmacology, dosage levels and circumstances of toxicity can be found in http://en.Wikipedia.org/wiki/acetaminophen [ref. 3].

APAP, like many other organic substances, undergoes an electrochemical “ec” mechanism. That is, the electron transfer step “e” produces a species that undergoes a follow-up chemical reaction “c” to produce either an electrochemically active or inactive product. Cyclic voltammetry is an ideal electrochemical method to probe this mechanism since the fate of the species produced in the forward scan can be ascertained during the reverse scan. The scan rate determines the time window for observation. The proposed oxidative mechanism [ref. 4] of APAP is shown in Figure 1.

Figure 1. Proposed ec mechanism for the oxidation of APAP

The initial step is the oxidation of APAP in a pH dependent, two-electron, two-proton step to produce N-acetyl-p-quinoneimine II (NAPQI). A typical cyclic voltammogram (CV) for APAP at pH 7 is seen in Figure 2. The experiment described herein is similar to an online one [ref. 5] and its embedded referrals to the original work by Kissinger and Heineman [6].

Figure 2. Cyclic Voltammogram of 2 mM APAP in pH 7.0 buffer at a glassy carbon electrode. Scan rate is 100 mV/s.

The anodic and cathodic waves are both well defined – the cathodic wave being shifted toward negative potentials due to a slower heterogeneous electron transfer rate of the quinoneimine. In acidic solutions, the follow-up equilibrium favors the protonated species III that undergoes rearrangement to the electroinactive species IV. Thus, the reverse cathodic wave is not observed, as illustrated in Figure 3, for CV of APAP at pH 2. If the scan rate is very fast, you may be able to “capture” species II, before it completely converts to species III, and observe a wave on the reverse scan.

Figure 3. Cyclic Voltammogram of APAP in pH 2 buffer at a Pt electrode. Scan rate is 100 mV/s.

The effect of solution pH and scan rate to cyclic voltammograms, and the determination of APAP in a Tylenol sample are the objectives of this experiment. An optional experiment, as described at the end of this section, is the calculation of the rate for the conversion of species III/IV to V, the benzoquinone.

The background to the basics of cyclic voltammetry is discussed in Concepts as linked from the main menu and in Experiment 1, titled Cyclic Voltammetry at Solid Electrodes.