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Keywords:

  • ammonium meta-vanadate;
  • benzoquinone;
  • creams;
  • hydroquinone;
  • spectrometry

Synopsis

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Material and methods
  5. Results and discussion
  6. Conclusion
  7. Acknowledgements
  8. References

A highly sensitive, simpler, faster and economical UV/visible spectrophotometric method has been established for the estimation of hydroquinone (HQ) in dilute organic matrices. The method is based on using ammonium meta-vanadate as an oxidizing catalyst for conversion of HQ to p-benzoquinone (BQ) in the presence of oxygen. As a result of higher absorption of UV light by BQ than by HQ, its signal has been utilized for determining HQ at the trace level. The effect of various parameters such as amount of oxidizing agent, stability time, temperature, acids and bases, solvents and interference by various compounds has been studied upon the absorption of BQ as HQ. Under optimized conditions, Beer’s Law was obeyed in the range of 0.025–2.00 μg ml−1 HQ at 245.5 nm using 1 : 1 (V/V) 2-propanol/water system with a lower detection limit of 7 ng ml−1 and linear regression coefficient of 0.9998. Relative standard deviation of 1.5% was observed for 0.5 μg ml−1 HQ solution (n = 11). The newly developed method has been successfully applied to diluted samples of various skin lightening creams for free HQ determination at the trace level. Comparison of the results obtained by the proposed method with those by a previously reported method proved its validity.

Résumé

Une méthode spectro photométrique UV/Visible très sensible, plus simple, plus rapide et économique a étéétablie pour l’évaluation d’Hydroquinone (HQ) dans des matrices organiques. La méthode est basée sur l’utilisation de l’ammonium meta-vanadate comme catalyseur d’oxydation pour convertir l’HQ en p-benzoquinone (BQ) en présence d’oxygène. En raison de la plus forte absorption en UV de la BQ que de l’HQ, son signal a été utilisé pour déterminer l’HQ à l’état de trace. L’effet de divers paramètres comme la quantité d’agent oxydant, la durée de stabilité, la température, les acides et les bases, les solvants et l’interférence de composés divers ont étéétudié sur l’absorption de la BQ comme de l’HQ. Dans les conditions optimales, la loi de Beer est respectée pour une gamme de 0.025 à 2.00 μG ml−1 d’HQ à 245.5 nm en utilisant un système 2-propanol/eau 1 :1 (V/V) avec une limite de détection de 7 ng ml−1 et un coefficient de régression linéaire de 0.9998. L’écart-type relatif de 1.5% a été observé pour une solution d’ HQ de 0.5 μG ml−1 (n =11). La nouvelle méthode a été utilisée avec succès pour des échantillons de crèmes éclaircissantes afin de déterminer l’HQ libre à l’état de trace. La comparaison des résultats obtenus par la méthode proposée avec ceux obtenus par celles précédemment proposées a permis de prouver sa validité.


Introduction

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Material and methods
  5. Results and discussion
  6. Conclusion
  7. Acknowledgements
  8. References

Hydroquinone (HQ) is used as a photographic developer [1], an antioxidant for fats and oils, a polymerization inhibitor, a stabilizer in paints, varnishes, motor fuels and oils, and an intermediate for rubber processing chemicals in the production of mono and dialkyl ethers [2]. It is extensively used in skin-toning preparations or skin lightening cosmetics and suggested to be effective at 1.5–2.0% [1, 3–6]. It is recommended that HQ must be used under prescription because its long-term contact in concentrations of greater than 5% can produce various side effects [4]. These side effects may be acute or chronic. Acute side effects are allergic and irritant contact dermatitis, post-inflammatory hyperpigmentation and nail discoloration. High concentrations of HQ (above 5–6%) have been implicated in persistent hypopigmentation or depigmentation, a condition known as leukoderma. Exogenous ochronosis is a major chronic side effect of HQ. This condition is characterized by reticulated, ripple-like, sooty pigmentation on the forehead, cheeks and other areas of HQ application [5]. Despite its numerous useful applications, HQ has been reported as mutagenic in animals [6] and a possible nephrocarcinogen [7].

Several techniques have been reported in the literature for estimation of HQ in cosmetics such as voltammetry [8, 9], high-performance liquid chromatography (HPLC) [6], chemiluminescence (CL) [1, 10], flow injection analysis [11], capillary electrochromatography (CEC) [12] and spectrophotometry [13]. Among all the techniques, the last one is considered faster and simpler. However, this technique has some limitations such as use of expensive and/or toxic ligands for complex formation, and hence its extensive use for HQ determination in aqueous samples [14–16]. The impracticality of spectrophotometry for HQ analysis in dilute samples of creams and cosmetics is attributable to its limited sensitivity and higher detection limits [13]. In this study, we report a highly sensitive, simpler, faster and economical spectrophotometric method for HQ determination in dilute organic matrices (skin lightening creams). The method could also be used to estimate HQ in aqueous samples using a solvent system, 2-propanol/water in a 1 : 1 (V/V) ratio.

Material and methods

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Material and methods
  5. Results and discussion
  6. Conclusion
  7. Acknowledgements
  8. References

Instrumentation

All UV–visible spectra were recorded using a Lambda 2 UV/Visible Spectrometer (Perkin-Elmer, GmbH, Germany).

Chemicals, solutions and glassware

Analytical grade chemicals, ammonium meta-vanadate (AMV) and HQ, were purchased from Merck (Darmstadt, Germany). Other analytical grade chemicals, solvents, acids and bases were purchased from the manufacturers, BDH (Poole, U.K.), Acros Chemicals (Geel, Belgium), Fluka (Buchs, Switzerland) and Sigma Aldrich (St. Louis, Missouri, MO, U.S.A.). Double-distilled water (DDW) was used in the preparation of all solutions. HQ solutions of required strength were prepared each day for routine work. The aqueous solution of 1000 μg ml−1 V (V) ions was prepared by adding appropriate quantity of AMV in about 70 ml of DDW followed by addition of 10 ml of 33% NH3 solution in a 100 ml volumetric flask. This mixture was sonicated until dissolution and made up to the mark with DDW. All glasswares were soaked in 3M HNO3 solution overnight and washed thoroughly first with tap water and then with detergent-containing water. Then the glasswares were thoroughly washed several times with tap water followed by rinsing three times with DDW and finally dried in an electric oven at 110°C.

Procedure

Appropriate volume of HQ solution was mixed with 0.025 ml of 100 μg ml−1 V (V) ions containing solution in a 10 ml volumetric flask. This mixture was diluted to 5 ml with DDW followed by 5 ml of 2-propanol and mixed well by thorough shaking. A blank solution was prepared in the same way but without HQ. The absorbance of instrument was set to zero in air at 200–500 nm. The solutions of analyte as well as the blank were rapidly transferred to 1-cm quartz cells, placed in the respective compartments and spectra recorded accordingly.

For the preparation of stock solution of lightening cream, 0.2 g of the sample was taken in a pre-weighed beaker and 2 ml of 2-propanol was added and thoroughly mixed using a glass rod. This mixture was filtered into a 10 ml volumetric flask. The remaining portion of the sample in the beaker was treated three times with 2 ml of 2-propanol and filtered each time through the same filter paper into the flask. The flask was made up to the mark with 2-propanol. Twenty microlitres of this solution was mixed with 0.025 ml of 100 μg ml−1 V (V) ions in a 10 ml volumetric flask. This mixture was diluted with DDW and 2-propanol such that a final ratio of 1 : 1 (V/V) was true. The sample thus prepared was transferred to the quartz cell and spectra recorded in the same way as mentioned above.

For a temperature-based experiment, the solutions of analyte as well as the blank were prepared in test tubes and placed in a water bath or freezing bucket at regulated desired temperature. Hot or cold water was added to the water bath or bucket for quick adjustment of the temperature.

Cream samples were also prepared according to the method reported earlier [3] and the results were compared with those of the newly developed method.

Results and discussion

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Material and methods
  5. Results and discussion
  6. Conclusion
  7. Acknowledgements
  8. References

Hydroquinone (HQ) is slowly oxidized to BQ via a semiquinone (SQ) radical in a buffered aqueous solution [17]. The active role of metals such as Cu (II) has been reported in case of the DNA damage study by describing the conversion of HQ to BQ via SQ [18]. The oxidizing property of Mn (VII) ions in a similar reaction has also been described in our previous work [16]. However, utmost care and skills are essential for achieving results in the lowest range. Furthermore, the mentioned method was applicable for determining HQ only in aqueous samples. In contrast, the newly developed method is capable of determining HQ in dilute organic samples (creams) efficiently irrespective of care.

Sensitivity enhancement

Results showing the conversion of HQ to BQ in the form of sensitive signal are shown in Fig. 1. Two UV signals are observed at λmax values of 288 and 222 nm representing absorbance by HQ and SQ, respectively, and are shown in Fig. 1a. The signal of SQ implies that the oxygen of the medium plays the role of a weak oxidizing agent to convert some part of HQ into SQ but unable to completely convert it into BQ. However, the addition of 1 μg ml−1 V (V) ions to HQ solution (Fig. 2b) results in the complete conversion of HQ into BQ as shown in Fig. 1b. Similar results have been described in the case of using Cu (II) ions [17]. These results prove that V (V) ions play multiple roles by (1) conversion of HQ to BQ, (2) conversion of existing SQ to BQ, (3) enhancement of absorbance for HQ determination in the form of BQ and (4) stability of the BQ signal.

image

Figure 1.  UV spectra of 0.5 μg ml−1 HQ solution showing a) HQ (288 nm) and SQ (222 nm) in the absence, and b) in the presence of 1 μg ml−1 V(V) ions.

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image

Figure 2.  Effect of concentration of V(V) ions on absorbance of 0.5 μg ml−1 HQ solution.

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In other words, the sensitivity of HQ determination has been enhanced in the form of stable BQ after the mediation of V (V) ions. The sensitivity in this case is greater than that seen in the case of Mn (VII) [16], where the peaks of HQ and/or SQ were also observed. The peak of BQ (Fig. 1b) is about five times greater than the actual peak observed with HQ (Fig. 1a). This means that V (V) ions catalyse the formation of BQ from SQ and HQ at a greater rate in the presence of O2. Similar studies have been reported earlier [16, 19].

Optimization of concentration of V (V) ions

Figure 2 shows the effect of V (V) ions in the concentration range of 0.1–2 μg ml−1 on the absorbance of 0.5 μg ml−1 solution of HQ at 245.5 nm based on its conversion to BQ after 5 min of mixing time at a room temperature of 25 ± 1°C.

The data show that the maximum absorbance of 0.14 is true for HQ as BQ after addition of 0.25 μg ml−1 V (V) ions. This may be attributed to the alkaline nature of the medium resulting from the addition of ammonium hydroxide during solution preparation (see experimental section), which also enhances the oxidation of HQ to BQ [17, 20]. An overall proposed reaction mechanism is thus given as:

inline image

Order of reagent addition

The order of addition of reagents plays a key role in peak enhancement [16]. In this study, it was noticed that addition of solution of 0.5 μg ml−1 HQ followed by 0.25 μg ml−1 V (V) ions and a final dilution to 10 ml gave poor absorbance at 245.5 nm. The order, water – HQ – V (V) also resulted in lower absorbance, while the maximum absorbance was true with the order, V (V) – HQ – water. Similar findings have been mentioned in previous studies [16, 21].

Optimization of mixing time

The dependence of change in absorbance on reagent mixing time is of prime importance in analytical chemistry as this factor determines the stability of the end product. Figure 3 shows the effect of time in the range of 3–60 min on the absorbance of 0.5 μg ml−1 of HQ solution as BQ at 245.5 nm in the presence of 0.25 μg ml−1 V (V) ions.

image

Figure 3.  Effect of time on absorbance of HQ as BQ at 245.5 nm.

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Absorbance values of 0.14, 0.13 and 0.12 were recorded for time ranges of 3–15 min, 20–35 min and 40–60 min respectively. The decreasing trend of absorbance with time in these ranges is indicative of a slow reversal of the process from BQ to HQ. However, 3 min was considered the optimum time and was preferred in further study. The effect of mixing time on absorbance has been reported previously [14, 16].

Effect of temperature

Figure 4 shows the effect of temperature in the range of 5–45°C on the absorbance of BQ resulting from 0.5 μg ml−1 of HQ solution at previously optimized parameters.

image

Figure 4.  Effect of temperature on absorbance of HQ as BQ.

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Maximum absorbance is observed for the temperature range of 5–15°C with decreasing trend for the ranges 20–30°C and 35–45°C, respectively. The greater absorbance value at lower temperature may be because of the condensed (cloudy) water vapours on the wall of quartz cell. This indicates a false positive result for HQ as BQ because of extra absorbance. The lower absorbance of HQ as BQ at higher temperature range is a result of evaporation of volatile ammonia with relative disturbance of optimal amount of V (V) ions. However, 25°C was considered the optimum temperature in order to avoid false reading arising from above-mentioned reasons. Dependence of absorbance on temperature has been described by other workers [14] and [16] for HQ determination, who have also recommended 25°C as the optimum temperature.

Effect of acidic and basic solutions

Table I shows the effect of various acids and bases on the absorbance of 0.5 μg ml−1 HQ as BQ solution at previously optimized conditions. It is observed that all the acids or bases have negative effect on the absorbance.

Table I.   Effect of some acids and bases on absorbance of 0.5 μg ml−1 HQ solution per 10 ml
Acid/base (0.1M)Volume of acid/base (ml)Absorbance% effect
  1. HQ, hydroquinone.

HCl0.10.08−42.8
1.00.09−35.7
CH3COOH0.10.13−7.1
1.00.10−28.6
H2SO40.10.10−28.6
1.00.09−35.7
Na2CO30.10.11−21.4
1.00.10−28.6
NaOH0.10.12−14.3
1.00.09−35.7

The negative effect observed in the case of HCl and H2SO4 solutions on absorbance of HQ as BQ is because of the back transformation of BQ into HQ in the presence of more H+ ions. Another reason may be the decrease in concentration of optimal ammonium ions occurring as a result of some extent of neutralization by these acids. The small effect of −7.1% by 0.1 ml of 0.1 M CH3COOH on the absorbance of HQ is because of its partial dissociation presenting minimum number of H+ ions and hence little reducing potential as compared with strong acids. However, its higher concentration increases its reducing capability for absorbance by BQ. In the case of 0.1 M Na2CO3 or NaOH, one expects higher absorbance of HQ as BQ because auto-oxidation of HQ to BQ occurs very rapidly at alkaline pH to produce a brown colour [17, 20]. However, as the medium is already alkaline because of the presence of NH3 in the solution, further increase in the amount of each base inhibits the oxidation of HQ favouring a reversal of the process at very high pH.

Effect of alcohols

Because of the unlimited solubility of methanol, ethanol and propanol [22], the effect of these solvents on the absorbance of HQ in alcohol: water system was studied. Table II shows the effect of these alcohols in the range of 1–7.5 ml per 10 ml of total solution on the absorbance of 0.5 μg ml−1 HQ solution.

Table II.   Effect of various solvents on absorbance of V(V)-treated 0.5 μg ml−1 HQ/10 ml solution
SolventVolume (ml)Absorbance% effect
  1. HQ, hydroquinone.

Methanol1.00.11−21.4
2.50.11−21.4
5.00.10−28.6
7.50.09−35.7
Ethanol1.00.12−14.3
2.50.11−21.4
5.00.11−21.4
7.50.10−28.6
2-Propanol1.00.1400.0
2.50.1400.0
5.00.140.00
7.50.13−7.1

The data show that 2-propanol has no interference from 1 to 5 ml concentration as compared with other alcohols. Based on this result, we extended this study for the determination of HQ in organic samples (skin lightening/bleaching creams). The decreased absorbance by methanol and ethanol is because of shorter hydrocarbon tails with more transparent nature compared with 2-propanol which has longer hydrocarbon tail and nearly same transparency at true for pure water. The effect of organic solvents on absorbance of HQ has been mentioned previously [16].

Interference effect

No interference was noticed for standard HQ solution in the presence of other ingredients such as glycolic acid, kojic acid, tretinoin, N-acetylcysteine, triamcinolone acetonide, alpha-arbutin and niacinamide taken per recommended ratio to HQ in creams.

Calibration plot

A linear calibration was observed for HQ solution in the range of 0.025–2.00 μg ml−1 with regression coefficient of 0.9998 under previously optimized parameters as shown in Fig. 5.

image

Figure 5.  Calibration curve of HQ in the range of 0.025 – 2.00 μg ml−1.

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A lower detection limit (LDL) of 7 ng ml−1 was true for HQ solution with 11 blank observations as per procedure described elsewhere [23]. The relative standard deviation of 1.5% was observed for 0.5 μg ml−1 HQ solution at n = 11. The newly investigated method shows good preference over other methods reported previously [10] where the linear ranges of 0.05–1.2 μg ml−1 and 0.04–0.18 μg ml−1 and LDL of 8 ng ml−1 and 7 ng ml−1, respectively, have been described for HQ solution. The proposed method has a further edge over other methods because of its simplicity, economy and faster analysis.

Application of the method developed

The newly developed method was used for the estimation of HQ in samples of various skin whitening creams. The results for all cream samples with 2% and 4% HQ on the label are listed in Table III. The validity of the current method in the estimation of HQ was checked by comparing its results with those obtained by a previously reported UV–visible spectrometric method [3]. However, lower dilution of the sample was used in the case of the latter method because of its lower sensitivity as compared with the currently developed method, where higher dilution was carried out because of greater sensitivity. The results were calculated as 95% confidence limits described elsewhere [23].

Table III.   HQ estimation in various locally available skin whitening creams
Cream SampleHQ on labelHQ determined (μg ml−1) n = 5
By developed methodBy Reported Method Actual (%)
Observed (μg ml−1)Actual (%)
  1. n = no. of replications, ± = standard deviation

  2. HQ, hydroquinone.

12%0.790 ± 0.0201.975 ± 0.0501.900 ± 0.050
20.820 ± 0.0102.050 ± 0.0251.950 ± 0.080
30.840 ± 0.0402.100 ± 0.1002.000 ± 0.100
40.780 ± 0.0301.950 ± 0.0751.900 ± 0.070
50.770 ± 0.0101.925 ± 0.0251.900 ± 0.100
64%1.620 ± 0.0404.050 ± 0.1003.900 ± 0.150
71.650 ± 0.0304.125 ± 0.0754.100 ± 0.100
81.580 ± 0.0503.950 ± 0.1254.050 ± 0.120
91.580 ± 0.0503.950 ± 0.1253.950 ± 0.160
101.600 ± 0.0604.000 ± 0.1504.150 ± 0.180

The similarity of results obtained by the proposed method with those obtained by the previously reported method [3] as shown in Table III suggests the good reproducibility and validity of the former method for application in the analysis of HQ in creams.

Conclusion

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Material and methods
  5. Results and discussion
  6. Conclusion
  7. Acknowledgements
  8. References

The results show that the newly investigated method is very useful for HQ determination in dilute samples of creams or cosmetics. The major advantages of the developed method are as follows: economical, simpler, faster and highly sensitive. The method could be equally helpful for HQ analysis in aqueous samples.

Acknowledgements

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Material and methods
  5. Results and discussion
  6. Conclusion
  7. Acknowledgements
  8. References

Technical and financial support by NCEAC, University of Sindh, Jamshoro is highly acknowledged.

References

  1. Top of page
  2. SynopsisRésumé
  3. Introduction
  4. Material and methods
  5. Results and discussion
  6. Conclusion
  7. Acknowledgements
  8. References
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