2746 J. Sep. Sci. 2013, 36, 2746–2752 Peter Q. Tranchida 1 Flavio A. Franchina 1 Mariosimone Zoccali 1 Ivana Bonaccorsi 1 Francesco Cacciola 2,3 Luigi Mondello 1,4 1 Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute, Universit ` a degli Studi di Messina, Messina, Italy 2 Dipartimento di Scienze dell’Ambiente, della Sicurezza, del Territorio, degli Alimenti e della Salute (S.A.S.T.A.S.), Universit ` a degli Studi di Messina, Messina, Italy 3 Chromaleont s.r.l. A spin-off of the University of Messina, c/o Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute, University of Messina, Messina, Italy 4 Centro Integrato di Ricerca (C.I.R.), Universit ` a Campus Bio-medico, Roma, Italy Received April 23, 2013 Revised May 31, 2013 Accepted May 31, 2013 Short Communication A direct sensitivity comparison between flow-modulated comprehensive 2D and 1D GC in untargeted and targeted MS-based experiments The present contribution is focused on the measurement of the analytical sensitivity attained in untargeted/targeted MS/MS experiments, performed using flow-modulator comprehen- sive 2D and 1D GC. The comprehensive 2D experiment was performed by diverting part of the high flow (circa 80%) to flush the accumulation loop (about 28 mL/min) to waste, to reduce the gas flow entering the ion source. 1D analyses were performed through: (i) unmodulated and (ii) single column applications. An equivalent temperature program was applied in the modulated and unmodulated analyses, while a faster one was employed in the single column one. In all application types, the (same) triple quadrupole instrument was op- erated in the full-scan and multiple reaction monitoring modes. A genuine sweet orange oil and the same sample spiked with 20 phytosanitary compounds were employed to reach the research objective. The results highlight the problems related to the flow modulation–MS combination. Specifically, it was found that sensitivity was on average three to four times higher in unmodulated and optimized single-column applications. Keywords: Citrus essential oil / Comprehensive GC / Flow modulation / Pesticide analysis / Triple quadrupole MS DOI 10.1002/jssc.201300423 1 Introduction In comprehensive 2D GC (GC×GC), a transfer system, ei- ther cryogenic or flow modulator (FM), has the function of fractionating and injecting primary-column chromatography bands onto a second analytical dimension, in a continuous and sequential manner. The possibility to subject second- wide segments (typically in the 2–8 s range) of primary col- umn effluent to a further separation on a stationary phase with a different selectivity greatly enhances both peak capac- ity and selectivity. In terms of sensitivity, the use of cryogenic fluids has a demonstrated beneficial effect; specifically, the principal ef- fect of cryogenic modulation is the compression (or focusing) of first-dimension chromatography bands in space. In fact, the first cryogenic modulator (LMCS: longitudinally modu- lated cryogenic system) was previously exploited to enhance Correspondence: Professor Luigi Mondello, Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute, Universit` a degli Studi di Messina, viale Annunziata, 98168 Messina, Italy E-mail: lmondello@unime.it Fax: +39-090-358220 Abbreviations: APC, advanced pressure control; FID, flame ionization detection; FM, flow modulator; GC×GC, compre- hensive two-dimensional gas chromatography; HCH, hex- achlorocyclohexane; IL, ionic liquid; MRM, multiple reaction monitoring; QqQ, triple quadrupole sensitivity prior to detection [1]. Whatever type of detector is employed (mainly flame ionization detection (FID) or MS), such a reconcentration effect will increase S/N. FID systems are mass-flow-dependent detectors, and depend on the mass of analyte per unit of time such devices receive. MS instru- ments are, on the contrary, concentration-sensitive detectors, and depend on the analyte concentration in the gas phase. Flow modulation was first described by Bruckner et al., who employed a six-port diaphragm valve to perform single- stage GC×GC modulation [2]. The first combination of FM- GC×GC with a TOF-MS instrument was reported in 2003 [3]: a high speed six-port diaphragm valve was equipped with a 5 L accumulation loop. At the beginning of the analysis, a flow of approximately 6.8 mL/min (circa 300 cm/s) was gen- erated in the second dimension, a value within the pumping capacity (maximum limit: 10 mL/min) of the TOF-MS. At present, the only commercial FM is a dual-stage one, constructed using capillary-flow technology [4] and based on the model proposed by Seeley et al. [5]. The FM is charac- terized by a planar metallic structure containing an internal accumulation chamber, which is filled with first-dimension effluent when the modulator is in the collection state; at the end of the collection period, the chamber content is flushed onto the second column (flush state) by using a very high gas flow (e.g., 20–25 mL/min). If one searches through the FM-GC×GC literature, then it becomes apparent that not many papers have described the use of MS detection. For example, Gu et al. analyzed C  2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.jss-journal.com