Abstract
Para-phenylenediamine (PPD) is a common chromophoric ingredient in oxidative hair-dyes. In some African countries like Sudan, Egypt and Morocco but also in India this chemical is used alone or in combination with colouring extracts like Henna for dyeing of the hair or the skin. Excessive dermal exposure to PPD mainly leads to the N-mono- and N,N′-diacetylated products (MAPPD, DAPPD) by N-acetyltransferase 1 and 2 (NAT1 and 2) catalyzed reactions. Metabolites and PPD are mainly excreted via renal clearance. Despite a low risk of intoxication when used in due form, there are numerous cases of acute intoxication in those countries every year. At the ENT Hospital - Khartoum (Sudan) alone more than 300 cases are reported every year (∼10% fatal), mostly caused by either an accidental or intended (suicidal) high systemic exposure to pure PPD. Intoxication leads to a severe clinical syndrome including laryngeal edema, rhabdomyolysis and subsequent renal failure, neurotoxicity and acute toxic hepatitis. To date, there is no defined clinical treatment or antidote available and treatment is largely supportive. Herein, we show the development of a quick on-site identification assay to facilitate differential diagnosis in the clinic and, more importantly, the implementation of an advanced analytical platform for future in-depth investigations of PPD intoxication and metabolism is described. The current work shows a sensitive (∼25 µM) wet chemistry assay, a validated MALDI-MS/MS and HPLC-UV assay for the determination of PPD and its metabolites in human urine. We show the feasibility of the methods for measuring PPD over a range of 50–1000 µM. The validation criteria included linearity, lower limit of quantification (LLOQ), accuracy and precision, recovery and stability. Finally, PPD concentrations were determined in clinical urine samples of cases of acute intoxication and the applied technique was expanded to identify MAPPD and DAPPD in the identical samples.
Highlights
Since the end of the 19th century the chemical p-phenylenediamine (PPD) has been described as a hair dye
Further structural information for the confirmation of the metabolites was provided by a MS2 product ion scan on the MALDI-QqQ and by a TOF/TOF spectrum with accurate masses
The current work describes the systematic approach for an indepth investigation of PPD intoxication, treatment effects and metabolism
Summary
Since the end of the 19th century the chemical p-phenylenediamine (PPD) has been described as a hair dye. In many African countries like Sudan, Egypt and Morocco, PPD in its pure form or in combination with other natural colouring extracts like Henna (e.g.: Black Henna) is used for colouring of skin (e.g.: palms and soles) for cosmetic reasons [3,4]. In these developing and other newly industrialized countries (e.g.: India) there are vast numbers of unintended and intended incidents of severe to life threatening intoxication involving this synthetic compound every year [4,5].
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