Gas chromatography–negative-ion chemical ionization mass spectrometry of hydrolysed human urine and blood plasma for the biomonitoring of occupational exposure to 4,4′-methylenebisaniline

Abstract

A gas chromatographic–mass spectrometric (GC–MS) method for the biological monitoring of 4,4′-methylenebisaniline (MDA), is presented. MDA was determined in urine and plasma after hydrolysis and analysed as the pentafluoropropionic anhydride derivative. High sensitivity and selectivity were achieved using negative-ion chemical ionization with ammonia as the reagent gas. The hydrolysis procedures for urine and plasma samples were studied under alkaline and acidic conditions. Alkaline conditions gave the highest recovery for both urine and plasma samples. Hydrolyses of urine at 80 °C and of plasma at 100 °C for 16 h were selected owing to the good recovery and precision achieved. Ten analyses of a urine sample containing 11 nmol l^–1 of MDA gave relative standard deviations (s_r) within and between assays of 2 and 6%, respectively. The determination of MDA in a plasma sample containing 8 nmol l^–1 of MDA gave s_r= 4 and 6% within and between assays, respectively (n= 5). For the preparation of samples spiked to 10 nmol l^–1 of MDA, the recovery was 97 ± 3% for urine samples and 96 ± 2% for plasma samples. The detection limit, defined as the blank plus three times the standard deviation of the blank, was 0.2 nmol l^–1 for aquous solutions containing an internal standard. Determinations of MDA in urine and plasma from exposed workers showed that the method is appropriate for biomonitoring.