947 Paal Molander a,b) , Anette Thomassen b) , Elsa Lundanes b) , Geir Fladseth a) , Syvert Thorud a) , Yngvar Thomassen a) , Tyge Greibrokk b) a) National Institute of Occupational Health, P.O.Box 8149 Dep, N-0033 Oslo, Norway b) Department of Chemistry, University of Oslo, P.O.Box 1033 Blindern, N-0315 Oslo, Norway Determination of 1-(2-methoxyphenyl)-piperazine derivatives of airborne diisocyanates by packed capillary liquid chromatography with pre-column large-volume enrichment A reliable, sensitive, and robust two-valve column-switching temperature-program- med packed capillary liquid chromatography method with on-column ultraviolet detec- tion has been developed and validated for the simultaneous determination of 2,4- toluene-diisocyanate, 2,6-toluene-diisocyanate, hexamethylene-diisocyanate, and 4,4-methylene-bisphenyl-diisocyanate in workroom air, based on an established 1-(2- methoxyphenyl)-piperazine derivatization filter sampling method. The isocyanate derivatives were enriched on a 0.32630 mm 5 lm Inertsil C 8 pre-column using a non-eluting solvent composition of acetonitrile-10 mM ammonium formate (pH 4.0) (4 : 96, v/v) at a flow rate of 50 lL/min, prior to back-flushing on a 0.32 6 250 mm 3-lm Hypersil ODS column, using a mobile phase composition of acetonitrile-10 mM ammonium formate (pH 6.0) (40 : 60, v/v) at a flow rate of 5 lL/min. Injection volumes up to 1.0 mL were loaded onto the pre-column. An initial temperature of 808C provi- ded beneficial selectivity effects as compared to ambient temperature, providing baseline separation of the 2,6-toluene-diisocyanate and hexamethylene-diisocyanate derivatives. Temperature programming from 80 to 958C provided efficient elution of late eluting 4,4-methylene-bisphenyl-diisocyanate. The method was validated using spiked filters with 5 to 250 ng of the 2,4-toluene-diisocyanate derivative, yielding a coefficient of correlation of 0.997 when using an injection volume of 1.0 mL. The within-assay (n = 4) and between-assay (n = 4) precisions were in the range 2.7 – 29.0 and 2.0 – 18.0%, respectively, and the within- and between-assay recoveries of the isocyanate derivatives were 92.3 – 97.8 and 95.4 – 96.7% for all concentrations except for the lowest level. The mass limit of detection of the isocyanate derivatives for the LC method was in the range 0.12 – 0.25 ng, corresponding to a concentration limit of detection of 12 – 23 ng/m 3 total isocyanate groups in air using a 15-L air samp- ling volume, with 20% sample exploitation, 100% sampling efficiency, and 50% reco- very at low concentrations. Key Words: Isocyanates; Air monitoring; Liquid chromatography; Packed capillary columns; Column switching; On-column focusing; Temperature programming; Ms received: July 10, 2001; revised: September 11, 2001; accepted: September 12, 2001 1 Introduction Isocyanates are major industrial chemicals, and their widespread use is related to their important role as raw materials for the production of polyurethanes to form foams, paints, lacquers, inks, insulating materials, varnishes, rubber modifiers, and bonding- and vulcanizing agents [1]. 2,4-Toluene-diisocyanate (2,4-TDI), 2,6- toluene-diisocyanate (2,6-TDI), hexamethylene-diisocya- nate (HDI), and 4,4-methylene-bisphenyl-diisocyanate (MDI) (Figure 1) are among the most frequently used iso- cyanates in such products [1]. Unfortunately, isocyanates are highly toxic substances that act as respiratory irritants and skin- and respiratory sensitizers, with the possibility of causing diseases like bronchitis, pulmonary emphysema, and asthma [2 – 4] in addition to allergic reactions [3]. Furthermore, isocyanates have a mutagenic potential through their ready reaction with proteins and DNA to form adducts [5]. Thus, the monitoring of isocyanates in workroom air is important to industrial hygiene. Isocyanates are highly reactive, and HDI and the TDI iso- mers are volatile. Thus, sampling methods for isocya- nates in workroom air usually include a derivatization step in which a volume of air is pumped through an impinger J. Sep. Sci. 2001, 24, 947–954 Correspondence: Dr. Paal Molander, NIOH, P.O.Box 8149 Dep, N-0033 Oslo, Norway. E-mail: pal.molander@stami.no Fax: +47 23 19 52 06 Original Paper i WILEY-VCH Verlag GmbH, D-69451 Weinheim 2001 1615-9306/2001/1212–0947$17.50+.50/0