Rapid determination of para-phenylenediamine by gas chromatography–mass spectrometry with selected ion monitoring in henna-containing cosmetic products

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Abstract

A rapid method for the determination of para-phenylenediamine (PPD) in cosmetic products, such as henna tattoos has been developed and evaluated. This analytical procedure involved extracting a 10 mg test portion of cosmetic product in 10 mL of ethyl acetate, followed by determination by gas chromatography–mass spectrometry in the selected ion monitoring mode (GC/MS-SIM). 1,4-Phenylenediamine-2,3,5,6-d4 was selected as an internal standard that was added at the beginning of the extraction procedure and used to correct for recovery and matrix effects. The linearity ranged from 1.0 to 1275 μg/mL with a coefficient of determination (r2) greater than 0.999. LOQ and LOD were 1.0 and 0.10 μg/mL, respectively. The recovery in a tattoo product containing PPD was 94% and that for a tattoo product containing no PPD reached 105%. Extraction efficiency of 98% was obtained. This method has been successfully applied to henna temporary tattoo and other henna-related cosmetic products for the determination and quantitation of PPD.

Introduction

Decorative tattoos have existed for thousands of years. Tattooing was primitively practiced for embellishment. However, it can represent a sign of distinction or social rank in some cultures and customs. Today, temporary henna tattoos applied to the skin are very fashionable and have become globally popular [1], [2], but this has been accompanied by more allergic reactions [3]. Henna is a natural product and itself has a relatively low allergic potential. It was reported that the allergic reactions are mostly caused by some ingredients added by the so-called “artists” [1]. The ingredients are generally coloring agents such as diaminotoluenes and diaminobenzenes. Para-phenylenediamine (PPD) is a typical diaminobenzene (Fig. 1) and is one of the most popular ingredients [4].

The allergic reactions caused by PPD include acute inflammatory reactions, eczematous hypersensitivity reactions, photo-aggravated reactions, granulomatous reactions, lichenoid reactions and pseudolymphomatous reactions [1], [2], [4], [5], [6], [7]. It was reported that the long duration of skin contact, the high concentrations of sensitizing materials, and the lack of a neutralizing agent dramatically increases the risk of skin sensitization [1], [2], [4], [5], [7]. Therefore, the Food and Drug Administration (FDA) approves henna only for use as a hair dye, not for direct application to the skin, as in the body-decorating process known as mehndi [8]. The unapproved use of a color additive makes these products adulterated and therefore illegal. PPD is a chemical substance, which is widely used as a permanent hair dye. It may also been found in textile or fur dyes, dark colored cosmetics, temporary tattoos, photographic developer and lithography plates, photocopying and printing inks, intermediates in the manufacture of antioxidants and accelerators for rubbers, oils, greases and gasoline. This chemical has traditionally been used for the coloration of hair and temporary tattoo [1]. The use of PPD as a hair dye is popular because it is a permanent dye that gives a natural look. Due to its high toxicity (lethal dose in rats is 80 mg/kg orally), PPD has been controlled for sale to the public [3], [9].

As far as analytical methods for PPD are concerned, gas chromatography (GC) has some restrictions for the determination of the hydrophilic substance in cosmetic products due to its high polarity and low volatility unless PPD is subject to derivatization, which is a tedious process [5], [10]. In recent years, high performance liquid chromatography (HPLC) was the most convenient method for the determination of these dye intermediates. However, the mobile phase contains 1,8-diaminooctane or triethylamine as an amine modifier and sodium heptane sulfonate as counterion to solve asymmetric and tailing problems [10]. For the liquid chromatographic (LC) separation, if an ultra visible/visible (uv/vis) detector is used, interference will affect the detection. If a liquid chromatography/mass spectrometry (LC/MS) method is used, the buffer agents are not compatible. Therefore, HPLC methods have some limitations as well.

The aim of this study was to develop a novel gas chromatography–mass spectrometry with selected ion monitoring (GC/MS-SIM) method to identify and quantitate the PPD in henna tattoo products. Since stable isotopically labeled PPD-d4 was used, any loss in the sample preparation and signal instability during a GC/MS run were compensated. A significant benefit of this method is that no time-consuming clean-up process is involved. This is the first method that uses a stable isotopically labeled standard for PPD in cosmetic products. This method can be also applied to other cosmetic products that contain PPD.

Section snippets

Chemicals

Reagent grade ethyl acetate was purchased from Fisher Scientific (Pittsburgh, PA, USA). Para-phenylenediamine, and para-phenylenediamine-2,3,5,6-d4, were purchased from Sigma–Aldrich (St. Louis, MO, USA). All of the chemicals were used without further purification.

Stock solution preparation for PPD and PPD-d4

A solid standard was accurately weighed into a volumetric flask to which ethyl acetate was added. Sonication was needed to accelerate the dissolution. A working PPD solution was used to make calibration standards. The stock solution

Ionization of PPD and PPD-d4

Total ion chromatogram (TIC) and electron impact (EI) spectra for PPD and PPD-d4 are presented in Fig. 2, Fig. 3, respectively.

For PPD quantitation, selected ion monitoring mode (SIM) was applied. The selected ions (m/z) for PPD were 108, 80 and 53; and the ions m/z 112, 84 and 56 were selected for PPD-d4. The peak area of the selected ions was used in calculation of concentration.

Calibration and determination of PPD in henna products

A representative calibration curve (Fig. 4) was established by plotting the ratio of the peak areas of PPD and PPD-d

Conclusion

It is necessary that the stable isotopically labeled internal standard for PPD be used to provide accurate quantitation by compensating for matrix effects and recovery loss without developing laborious cleanup procedures or performing standard additions for each sample extract. To obtain high accuracy and avoid misleading values for the lower concentrations, a weighting factor 1/x2 (inverse square of concentration) should be applied to generate a calibration curve. The stability of standards at

Acknowledgement

Authors wish to thank Wayne Wamer, Jon Wong, Robert Bronaugh, and Don Havery (all from U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition) for helpful discussions.

References (10)

  • R.R. Brancaccio et al.

    Am. J. Contact Dermat.

    (2002)
  • J. Farrell et al.

    Toxicol. Lett.

    (2009)
  • J. Kazandjieva et al.

    Clin. Dermatol.

    (2007)
  • A. Ramírez-Andreo et al.

    Actas Dermosifiliogr. (Engl. Ed.)

    (2007)
  • M. Akyuz et al.

    J. Pharm. Anal.

    (2008)
There are more references available in the full text version of this article.

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