Methotrexate residues on the outer surface of medicine vials: from contamination assessment to the testing of two decontamination procedures

Context
Methotrexate (MTX), a cytotoxic drug used in ectopic pregnancies, is prepared either by the Pharmaceutical Technology Department or, outside working hours, by qualified nurses in the Obstetric Emergency Department. Residual contamination (RC) with MTX has already been detected on vials stored in this care unit.

Objectives
This study aimed to assess (1) the RC with MTX on the outer surface of MTX vials and (2) the effectiveness of two surface decontamination procedures.

Material and Methods
Surface samples were taken by wiping with a desorption solvent-soaked compress and then analysed by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. The detection and quantification limits were 1 and 2.5 pg of MTX/vial, respectively. Four series of 10 vials were analysed: S1 for the RC of the vial in three areas ((A) side contour and under the vial, (B) on the flip-off cover (FOC), (C) on the septum under the FOC), S2 for the RC of the entire vial with FOC; S3 and S4 for the decontamination procedures. The latter consisted of two successive decontamination steps (Surfanios IP sterile PAE Anios™ disinfectant detergent followed by 70 °C ethyl alcohol). S3 used a sterile compress and S4 a non-sterile single-use wipe. RC was expressed as median [Q1;Q3] pg/vial or pg/cm² and compared between groups using the Kruskal-Wallis test followed by Dunn’s post hoc test.

Results
Before decontamination (n=20, S1+S2), MTX RC was found on 100% of the MTX vials surface with a median RC of 367.5pg/vial [249.7-1609.9]. For S1, the median MTX RC in area C was significantly lower (1.4pg/cm² [0.5-4.7]) than in area A (26.5pg/cm², [11.4-82.8], p<0.001) and B (32.1pg/cm² [16.9-140.5), p<0.001). No significant difference was observed between aeras A and B (p=0.2627). It was then decided to keep the FOC to carry out decontamination.
After decontamination procedure (n=20, S3+S4), MTX RC was found on 100% of the MTX vials surface with a median RC of 6.6pg/vial [2.6-11.7] for S3 and 1.3pg/vial [0.8-3.6] for S4, both values were significantly lower than those before decontamination (S3 vs S1+S2 and S4 vs S1+S2, p<0.001). Between the use of a sterile compress (S3) or a non-sterile single-use wipe (S4), no significant difference was observed (p=0.2394).

Discussion-Conclusion
The MTX RC on the vials was more frequent (100%) than previously reported (15.1%) [1], possibly due to the higher sensitivity of our analytical method. Area under the FOC was the least contaminated area compared to other vial areas, which could indicate that the industrial decontamination process after FOC placement is only partially effective. Moreover, both tested decontamination procedures were effective in reducing MTX RC and may help limit occupational exposure.

Reference
[1] Hilliquin D, et al.. External contamination of commercial containers by antineoplastic agents: a literature review. Eur J Hosp Pharm 2020;27:313–4.

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