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Chromatographic Method for Determining 6‑Mercaptopurine in Skin Permeation Assays for Assessing Cutaneous Exposure
Gabriel S Oliveira1, Ana Luiza Lima1, Idejan P Gross1
1Laboratory of Food Drugs, and Cosmetics (LTMAC) University of Brasilia, Brasília, DF 70910-900, Brazil.
ACS Omega
|August 4, 2025
Summary
Healthcare professionals face occupational risks from 6-Mercaptopurine monohydrate (6-MP) due to limited skin absorption data. This study developed a validated HPLC method to quantify 6-MP in skin, revealing significant retention and high dermal exposure risk.
Area of Science:
- Pharmacology and Toxicology
- Analytical Chemistry
- Dermatology
Background:
- Limited data exists on the cutaneous absorption of 6-Mercaptopurine monohydrate (6-MP), a leukemia chemotherapy drug.
- This knowledge gap raises concerns regarding occupational exposure risks for healthcare professionals and caregivers handling 6-MP.
Purpose of the Study:
- To validate a high-performance liquid chromatography (HPLC) method for quantifying 6-MP in skin tissue.
- To assess the cutaneous permeation and retention of 6-MP.
- To establish a reliable analytical tool for evaluating dermal exposure risks associated with 6-MP.
Main Methods:
- Development and validation of an HPLC method for 6-MP quantification in skin.
- Assessment of method selectivity, linearity (R=0.999), precision, and sensitivity (LOD=0.13 μg/mL, LOQ=0.39 μg/mL).
- Optimization of an extraction procedure to ensure reproducible drug recovery from skin layers.
- Preliminary skin permeation study using porcine skin model.
Main Results:
- The validated HPLC method demonstrated high selectivity, linearity, precision, and sensitivity for 6-MP in skin matrices.
- The extraction procedure effectively recovered 6-MP from the stratum corneum and deeper skin layers, minimizing enzymatic degradation.
- Preliminary tests on porcine skin indicated that 6-MP is primarily retained in the deeper skin layers, with approximately 2% of the applied dose accumulating within 30 minutes, suggesting significant dermal absorption.
Conclusions:
- The validated HPLC method is a crucial tool for assessing topical 6-MP contamination risks.
- Significant skin retention of 6-MP highlights a high potential for dermal exposure, necessitating stringent safety measures.
- Findings support the need for personal protective equipment and strict handling protocols to protect healthcare professionals, caregivers, and patients.
