A new sensitive sensor was fabricated for simultaneous determination of codeine and acetaminophen based on 4-hydroxy-2-(triphenylphosphonio)phenolate (HTP) and multiwall carbon nanotubes paste electrode at trace levels. The sensitivity of codeine determination was deeply affected by spiking multiwall carbon nanotubes and a modifier in carbon paste. Electron transfer coefficient,
Codeine (3-methyl morphine, see Scheme
Molecular structure of codeine.
Various reports have been found for the determination of codeine in real samples with different matrices. They are including gas chromatography-mass spectrometry [
Acetaminophen (paracetamol, N-acetyl-
Acetaminophen in combination with opioid analgesics like codeine can also be used in the management of more severe pain such as postsurgical pain and providing palliative care in advanced cancer patients and improving the efficacy for about 50% of patients [
All the electrochemical measurements were carried out using an Autolab potentiostat-galvanostat PGSTAT 30 (Eco Chemie, Netherlands) equipped with GPES 4.9 software. A three-electrode assembly was employed to the experiment in a 50 mL glass cell equipped with a HTP multiwall carbon nanotubes modified carbon paste electrode (HTP-MWCNT-CPE) as the working electrode, a graphite electrode as an auxiliary electrode, and a saturated calomel electrode, SCE, as a reference electrode. All of the potentials in the text are quoted versus this reference electrode. A personal computer was used for data storage and processing. A Metrohm 781 pH/mV meter was also used for pH measurements.
Codeine as codeine phosphate 1/2 H2O (Sigma, USA) and acetaminophen (Merck, Germany) with analytical grades were used as received. All of the solutions were freshly prepared using double-distilled water. Graphite fine powder (Fluka, Swiss) and paraffin oil (DC 350, Merck, density = 0.88 g cm−3) were used as binding agents for the graphite pastes. The multiwall carbon nanotube (MWCNT) with a diameter of 10–20 nm, length of 5–20
Modified carbon paste electrode was prepared in a conventional fashion by thoroughly hand-mixing of HTP (0.5 mg), MWCNT (1.0 mg), and graphite powder (100.0 mg) and in a mortar with a pestle. Paraffin was added to the mixture using a 5 mL syringe and mixed well to obtain a uniformly wetted paste. The HTP-MWCNT-CP electrode (HTP-MWCNT-CPE) was fabricated by packing the paste into the end of a Teflon rod (ca. 2 mm i.d. and 10 cm long) and leveled off with a spatula. Then, the electrical contact was made by inserting a copper wire into the Teflon rod at the end of the mixture. When necessary, a new surface was obtained by pushing an excess of paste out of the tube and polishing it on a white paper. HTP modified CPE (HTP-CPE) and multiwall carbon nanotubes modified carbon paste electrode (MWCNT-CPE) were made in the same way without adding MWCNT to the former and HTP to the carbon paste. Moreover, unmodified carbon paste electrode (CPE) was prepared by mixing graphite powder and paraffin to obtain a wetted paste and fabricated as discussed.
The human serum was collected from volunteers who had not taken codeine and acetaminophen. For purification, 5 mL of 10% CCl3CO2H was added to 5 mL of the serum, shaked, and centrifuged for 5 min at 5000 rpm. The sample was diluted 10 times by a 0.15 M phosphate buffer solution at pH 7.0 and was treated just after spiking of codeine and acetaminophen according to the given procedure by DPV technique.
Fresh human urine samples were obtained from different volunteers who had not taken codeine and acetaminophen. Each sample was diluted 30 times by a 0.15 M phosphate buffer solution at pH 7.0 after filtering using Whatman filter paper (number 1). The electrochemical determination of codeine was done after spiking suitable amounts of codeine using DPV technique.
Five acetaminophen tablets (in dose of 325 mg and 500 mg) acetaminophen-codeine (325–10 mg) were powdered and mixed thoroughly. An amount corresponding to a tablet was weighed, dissolved with 10.0 mL of water, and sonicated for 3 min. The sample was filtered through a Whatman filter paper (number 1), transferred to a 25 mL volumetric flask, and diluted to the mark with phosphate buffer solution at pH 7.0. A suitable aliquot of the solution was used for analysis using the procedure. Also, the sample was spiked with different amounts of codeine and acetaminophen and quantified using DPV technique.
The activity of MWCNT and HTP as a modifier and the potential of electrocatalytic oxidation of codeine at the surface of different modified electrodes including MWCNT-CPE, HTP-CPE, and HTP-MWCNT-CPE was investigated by recording the cyclic voltammograms in the absence and presence of 0.11 mM of codeine solution and comparison of them with the same voltammograms was recorded at the CPE. The electrocatalytic activity is discussed in detail as follows: voltammograms of (a) and (b) of Figure
Cyclic voltammograms of (a) CPE, (c) MWCNT-CPE, (e) HTP-CPE and (g) HTP-MWCNT-CPE in a 0.15 M phosphate buffer solution (pH 7.0). (b) as (a), (d) as (c), (f) as (e) and (h) as (g) in presence of 0.11 mM of codeine. Scan rate: 25 mV s−1.
Cyclic voltammograms of HTP-CPE in codeine-free electrolyte, 0.15 M of a phosphate buffer solution at pH 7.0 (voltammogram (e)), and 0.11 mM of codeine (voltammogram (f)) at the scan rate potential of 25 mV s−1 were recorded. As it can be seen, codeine oxidizes at 274 mV at HTP-CPE surface, while the anodic peak current for oxidation of codeine at MWCNT-CPE is about 550 mV. Moreover, the anodic peak current increased to 0.545
Figure
Cyclic voltammograms of HTP-MWCNT-CPE in a 0.15 M phosphate buffer solution (pH 7.0) containing 0.11 mM of codeine at different scan rates. The numbers of 1–10 correspond to scan rates of 2.5, 5, 7.5, 10, 12.5, 15, 17,5, 20, 22.5, and 25 mV s−1. Insets: (a) variation of the electrocatalytic peak currents versus the square root of scan rate and (b) variation of the scan rate normalized peak current (
Cyclic voltammograms of HTP-MWCNT-CPE in a 0.15 M phosphate buffer solution (pH 7.0) containing 0.11 mM of codeine at scan rates 2.5, 5, 7.5, and 10 mV s−1. The circles show the part of cyclic voltammograms that was used for deriving Tafel plot. Inset shows the Tafel plots derived from the circled current-potential curve recorded at scan rates of 2.5, 5, 7.5, and 10 mV s−1.
For slow potential scan rates,
Figure
Chronoamperometry technique was used for the determination of apparent diffusion coefficient of codeine at HTP-MWCNT-CPE surface under working experimental conditions. Chronoamperograms were obtained by setting the working electrode potential at 235 mV for various concentrations of codeine (Figure
Chronoamperometric current responses at HTP-MWCNT-CPE surface in a 0.15 M phosphate buffer solution (pH 7.0), at a step potential of 235 mV, for different concentrations of codeine. The numbers of 1–5 correspond to 0.02, 0.04, 0.06, 0.08, and 0.1 mM of codeine. Insets: (a) plots of
Based on the Cottrell equation, the plot of
Since differential pulse voltammetry (DPV) has much higher current sensitivity and selectivity than cyclic voltammetry does, it was used to estimate the linear range, detection limit, and individual quantification of codeine and to simultaneously determine codeine and acetaminophen in various real samples. The effect of increasing the concentration of codeine in the range of 0.2–34.1
Comparison of the efficiency of different modified electrodes for the determination of codeine.
Electrode name | Detection method | Modifier | Linear range ( |
Detection limit ( |
Sensitivity ( |
Real sample | Reference |
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SWCNT/CCEa | DPVh | SWCNT | 0.2–230.0 | 0.11 | 0.1959 | Pharmaceutical samples, soft drinks, and urine | [ |
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BBDEb | Amperometry | — | 26.72–133.63 | 0.45 | 1.79 | Pharmaceutical samples | [ |
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GR-NF/GCEc | SWVi | 0.05–30.0 | 0.015 | 16.20 | Pharmaceutical samples and urine | [ | |
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DNA/MWCNT-PDDA/PGEd | DPV | 0.17–133.6 | 0.14 | 2.6508 | Drug formulations, urine, and plasma | [ | |
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BDDFEe | DPV | — | 0.1–60.0 | 0.08 | 0.155 | Human urine | [ |
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PB/Pd-Al Ef | DPV | PB | 2.0–30.0 | 0.8 | 0.078 | Synthetic sample | [ |
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HTP-MWCNT-CPEg | DPV | HTP | 0.2–34.1 |
0.063 | 0.0288 |
Pharmaceutical formulations, urine, and plasma | This work |
(a) and (b) show differential pulse voltammograms of HTP-MWCNT-CPE in a 0.15 M phosphate buffer solution (pH 7.0) containing different concentrations of codeine. The numbers of 1–19 and 20–34 correspond to 0.2–31.4
The utility of the modified electrode was studied for the simultaneous determination of codeine and acetaminophen by simultaneously changing the concentrations of codeine and acetaminophen. The voltammetric responses show that the simultaneous determination of codeine and acetaminophen with two anodic peaks at potentials of 170 and 410 mV, corresponding to the oxidation of codeine and acetaminophen, is possible at HTP-MWCNT-CPE (Figure
(a) Differential pulse voltammograms of HTP-MWCNT-CPE in a 0.15 M phosphate buffer solution (pH 7.0) containing different concentrations of codeine and acetaminophen. The numbers 1–21 correspond to 1.3–168.2
Applicability and selectivity of the developed procedure were also evaluated by studying the effect of some common species that often accompany codeine in real samples. The study was performed by analyzing of 40.0
Interference study of some species for the determination of 40.0
Foreign species | Molar ratio (foreign species/codeine) |
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Na+, K+, Ca2+, Cl−, and |
1000 |
Urea | 695 |
Uric acid | 675 |
Methadone, Tramadol | 310 |
Morphine | 5 |
Ascorbic acid | 1 |
The evaluation of reliability and applicability of the developed procedure makes potential usefulness for quantitative determination of codeine and acetaminophen in samples with different matrices. Human serum and urine samples were selected as biological samples. After sample preparation as discussed in Sections
Determination of codeine in human urine and serum samples using HTP-MWCNT-CPE.
Sample | Added ( |
Founda ( |
RSD (%) | Recovery (%) | ||||
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COD | AC | COD | AC | COD | AC | COD | AC | |
Serum | — | — | <DL | <DL | — | — | — | — |
10.0 | 20.0 | 10.1 ± 0.1 | 19.9 ± 0.2 | 1.1 | 1.0 | 100.8 | 99.6 | |
20.0 | 20.0 | 19.9 ± 0.2 | 20.2 ± 0.2 | 1.0 | 1.0 | 99.4 | 101.0 | |
40.0 | 60.0 | 40.2 ± 0.4 | 59.9 ± 0.6 | 1.0 | 1.0 | 100.5 | 99.8 | |
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Urine | — | — | <DL | <DL | — | — | — | — |
10.0 | 20.0 | 9.9 ± 0.1 | 20.2 ± 0.2 | 1.1 | 1.0 | 99.1 | 100.9 | |
20.0 | 20.0 | 20.1 ± 0.2 | 20.1 ± 0.2 | 1.0 | 1.0 | 100.6 | 100.6 | |
40.0 | 60.0 | 40.2 ± 0.4 | 59.9 ± 0.6 | 1.0 | 1.0 | 100.6 | 99.8 |
Also, acetaminophen tablets (in dosage of 325 and 500 mg) and acetaminophen-codeine tablets were used as pharmaceutical samples. Sample preparation was done as previously discussed in Section
Determination of codeine in pharmaceutical samples using HTP-MWCNT-CPE.
Sample | Added (mg) | Founda (mg) | RSD (%) | Recovery (%) | Labelled value | Statistical |
Company/batch number | ||||||
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COD | AC | COD | AC | COD | AC | COD | AC | COD | AC | COD | AC | ||
AC tablet | — | — | — | 324.2 ± 3.3 | — | 1.0 | — | 99.7 | — | 325.0 | — | 0.5 | Jalinous/92046 |
10.0 | — | 9.9 ± 0.1 | 324.2 ± 3.3 | 1.0 | 1.0 | 99.1 | — | — | — | — | — | ||
15.0 | 10.0 | 15.1 ± 0.2 | 335.2 ± 3.4 | 1.0 | 1.0 | 100.7 | 100.0 | — | — | — | — | ||
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AC tablet | — | — | — | 504.1 ± 5.0 | — | — | — | 100.8 | — | 500.0 | — | 1.6 | Soha/91025 |
10.0 | — | 10.1 ± 0.1 | 503.0 ± 5.0 | 1.1 | 1.0 | 101.2 | — | — | — | — | — | ||
15.0 | 25.0 | 14.9 ± 0.2 | 526.1 ± 5.2 | 1.0 | 1.0 | 99.2 | 100.2 | — | — | — | — | ||
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AC-COD tablet | — | — | — | — | — | — | — | — | 10 | 300.0 | — | — | Pharmachemie/071 |
— | — | 10.1 ± 0.1 | 298.9 ± 3.1 | 1.1 | 1.0 | 100.8 | 99.6 | — | — | 1.4 | 0.7 | ||
5.0 | — | 14.9 ± 0.2 | 298.1 ± 3.2 | 1.0 | 1.1 | 99.4 | — | — | — | — | — | ||
— | 5.0 | 9.8 ± 0.1 | 306.0 ± 3.3 | 1.2 | 1.0 | 98.2 | 100.3 | — | — | — | — | ||
5.0 | 5.0 | 15.4 ± 0.2 | 304.1 ± 3.2 | 1.0 | 1.0 | 102.4 | 99.7 | — | — | — | — |
bTabulated value of
This study has demonstrated that the HTP-MWCNT-CPE can be applied for the quantitative determination of codeine. The results show that the combination of MWCNT and HTP improved the electrocatalytic oxidation characteristic of codeine. The mechanism of
The authors declare that there is no conflict of interests regarding the publication of this paper.