## 1 Introduction  
Several compounds in raw grapes have been linked to sensory attributes in wines, and thus may be useful for screening or sorting grapes based on intended wine quality [1, 2, 3]. One such odorant is 3-isobutyl-2-methoxypyrazine (IBMP, \"herbaceous, bell pepper aroma\") [4]. IBMP accumulates primarily in the skins of grape berries before veraison after which concentrations begin to decrease [4, 5]. IBMP is absent in the mature fruit of many cultivars, but may be found above recognition threshold (15 ng/L in red wine; or, <15 ng/kg assuming a density of wine of 1 g/mL) and contribute to the varietal character of Bordeaux varieties (e.g., Cabernet Sauvignon, Sauvignon blanc, Cabernet franc, and Merlot) [4, 5, 6]. However, at excess concentrations, IBMP can diminish wine fruitiness, which may be detrimental to consumer acceptance [7].  
As with other trace-level odorants in foodstuffs, the routine analysis of IBMP is complicated by its low concentration and the presence of many interfering compounds in the grape and wine matrix [8]. The extraction and preconcentration of IBMP and other odorants are often done by headspace solid phase microextraction (HS-SPME), as the approach requires no solvents and is readily automated [9, 10]. After SPME extraction, odorants are thermally desorbed in the heated inlet of a gas chromatograph-mass spectrometer (GC-MS) for separation and detection. This approach is well-established, and low ng/L or ng/kg detection limits are feasible [11], but throughput is limited by both the HS-SPME extraction step (5 min or longer) and chromatography step (20-60 min) [8].  
Solid-phase mesh-enhanced sorption from headspace (SPMESH) sheets coupled to direct analysis in real time mass spectrometry (DART-MS) has been reported as a rapid alternative to SPME-GC-MS for trace analysis of IBMP and other odorants [12; 13]. SPMESH sheets are a variant of thin-film microextraction and consist of thin sorbent material (e.g., PDMS) etched to make it compatible with transmission mode DART-MS [14]. During use, the SPMESH sheet is positioned above a loaded multiwell plate for parallel headspace extraction of volatiles. After extraction, the SPMESH sheet is transferred to an automated positioning stage for DART-MS analysis of extracted spots. Using grape samples, this workflow was able to achieve ng/L detection limits for IBMP in 24 samples in 17 min [13]. However, run-to-run repeatability in grape homogenate was relatively poor (coefficient of variation (CV) = 32%). Additionally, headspace leakage among adjacent wells ('crosstalk') was high, approximately 1.2%, which limited the dynamic range of the approach [13]. Finally, while validation of SPMESH-DART-MS against HS-SPME-GCMS using commercial vineyard samples show acceptable correlation (R\({}^{2}\) = 0.71) across an IBMP range of <2 to 28 ng/L (or <2 to 26 ng/kg, However, close inspection of the data reveals poor correlation between the methods when considered only those samples at or below the sensory threshold (<2 to 15 ng/L) [12; 13].  
The purpose of this study was (i) to develop an improved and fully optimized SPMESH-DART-MS/MS approach for quantitating IBMP at sub-ng/kg levels in grape homogenate by improving limit of detection and repeatability, (ii) to perform a large-scale validation study (\(n\) = 302) using grape samples from commercial vineyards, and (iii) to demonstrate the suitability of the approach on multiple MS detectors.