Limits of detection for the determination of mono- and dicarboxylic acids using gas and liquid chromatographic methods coupled with mass spectrometry

Abstract

The chromatographic separation and instrumental limits of detection (LODs) were obtained for a broad range of C(1)-C(18) monocarboxylic (MCAs) and C(2)-C(14) dicarboxylic acids (DCAs) employing either chemical derivatization followed by gas chromatography-mass spectrometry and flame ionization detection (GC-MS/FID) or direct analysis with liquid chromatography high resolution MS and tandem MS (LC-MS). Suitability, efficiency and stability of reaction products for several derivatization agents used for esterification (BF(3)/butanol), and trimethysilylation, including trimethylsilyl-N-N-dimethylcarbamate (TMSDMC) and N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) were evaluated. The lowest limits of detection for the majority of compounds below 10 pg (with the exception of acetic acid) were obtained for derivatization with BF(3)/butanol followed by GC-MS in the total ion current (TIC) mode. Further improvements were achieved when applying either selected ion monitoring (SIM), which decreased the LODs to 1-4 pg or a combination of SIM and TIC (SITI) (2-5 pg). GC-FID provided LODs comparable to those obtained by GC-MS TIC. Both trimethylsilylation (followed by GC-MS) and direct LC-MS/MS analysis yielded LODs of 5-40 pg for most of the acids. For volatile acids the LODs were higher, e.g., 25 and 590 ng for TMSDMC and BSTFA derivatized formic acid, respectively, whereas the LC-MS methods did not allow for the analysis of formic acid at all.

Figure 1

The optimization of TMSDMC derivatization conditions (temperature and time) compared to BSTFA derivatization (at 60 °C for 1h) for selected acids: 1a formic acid, 1b nonanoic acid, 1c heptadecanoic acid, 1e malonic acid, 1f pimelic acid, and 1g tridecanedioic acid.

Figure 2

Effect of aging on the BSTFA-derivatized samples: a) freshly derivatized sample, b) freshly derivatized shown in enlarged scale vs. c) 2-week old sample. The numbers #1–4 refer to BSTFA and its by-products described in Section3.3, C₁-C₅ symbols refer to monocarboxylic acids. For derivatization, the molar ratio of BSTFA to acids was 10:1.

Figure 3

Aging of a sample derivatized with trimethylsilyl dimethylcarbamate analyzed a) 15 min, b) 6 h, and c) 12 h after the derivatization. The arrows highlight the affected response, which can be compared to the response of the internal standard.

Figure 4

Effect of electrolyte addition on the electrospray ionization efficiency in TOF MS for mono- and dicarboxylic acids.