Methotrexate. Determination method in workplace air
Journal Title: Podstawy i Metody Oceny Środowiska Pracy - Year 2016, Vol 32, Issue 1
Abstract
Methotrexate (MTX) is solid at room temperature.It is a yellowish-orange, crystalline powder with aslight odor characteristic of aromatic compounds.Methotrexate is an antineoplastic drugcommonly used in the treatment of malignantdiseases. Occupational exposure to methotrexatemay occur during its production, preparationand application of methotrexate on oncologywards. In terms of exposure by inhalation,methotrexate can irritate the eyes and mucousmembranes of the nose. Other adverse effects ofmethotrexate include chill and fever, sweating,arthralgia, myalgia, decreased resistance toinfection, septicemia, upper respiratory infection,osteoporosis, hypogammaglobulinemia, cystitis,dysuria, vaginal discharge, diabetes and death.Exposure to methotrexate may also causemyelosuppression, hepatotoxicity and impairedfertility. Due to the growing use of methotrexate,number of persons occupationally exposed toits harmful effect may reach in Poland severalthousand.The aim of this study was to develop and validatea sensitive method for determining methotrexateconcentrations in workplace air in the range from1/10 to 2 MAC values, in accordance with therequirements of Standard No. PN-EN 482.The study was performed using a liquidchromatograph with tandem mass detection(HPLC-MS/MS). All chromatographic analyseswere performed with Supelcosil LC 18 150 × 3 mmanalytical column, which was eluted withamixture of methanol and water with 0.1% offormic acid.This method is based on the collection ofmethotrexate on a glass fi ber fi lter, extractionwith mixture of methanol and water withformic acid (0.1%), and chromatographic analysisof the resulting solution with HPLC-MS/MStechnique. The average extraction effi ciency ofmethotrexate from fi lters was 90%. This methodis linear (r = 0.999) within the investigatedworking range of 0.00007–0.0028 mg/m3 fora 720-L air sample. Limit of detection (LOD) andlimit of quantifi cation (LOQ) were 0.0013 and0.0044 μg/ml, respectively.The analytical method described in this paper,thanks to the use of HPLC MS/MS technique,makes it possible to selectively determinemethotrexate in workplace air in the presenceof other compounds at concentrations from0.00007 mg/m3 (<1/10 proposed MAC value).This method is precise, accurate and it meets thecriteria for procedures for measuring chemicalagents listed in Standard No. EN 482: 2006.This method can be used for assessing occupationalexposure to methotrexate and associated riskto workers’ health. The developed method ofdetermining methotrexate has been recorded asan analytical procedure (see appendix).
Authors and Affiliations
Sławomir Brzeźnicki, Marzena Bonczarowska, Karolina Mikołajewska
Keywords
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