Electrospray, high flow

In general terms, electrospray ionization is considered to be concentration-sensitive at Tow flow rates and mass-flow-sensitive at high flow rates, while APCI is considered to be mass-flow-sensitive. Low and high are both subjective terms and require investigation as part of method validation. 

As the vast majority of LC separations are carried out by means of gradient-elution RPLC, solvent-elimination RPLC-FUR interfaces suitable for the elimination of aqueous eluent contents are of considerable use. RPLC-FTTR systems based on TSP, PB and ultrasonic nebulisa-tion can handle relatively high flows of aqueous eluents (0.3-1 ml.min 1) and allow the use of conventional-size LC. However, due to diffuse spray characteristics and poor efficiency of analyte transfer to the substrate, their applicability is limited, with moderate (100 ng) to unfavourable (l-10pg) identification limits (mass injected). Better results (0.5-5 ng injected) are obtained with pneumatic and electrospray nebulisers, especially in combination with ZnSe substrates. Pneumatic LC-FI1R interfaces combine rapid solvent elimination with a relatively narrow spray. This allows deposition of analytes in narrow spots, so that FUR transmission microscopy achieves mass sensitivities in the low- or even sub-ng range. The flow-rates that can be handled directly by these systems are 2-50 pLmin-1, which means that micro- or narrow-bore LC (i.d. 0.2-1 mm) has to be applied. 

Chiron S, Papilloud S, Haerdi W, Barcelo D (1995) Automated online liquid-solid extraction followed by liquid chromatography-high-flow pneumatically assisted electrospray mass-spectrometry for the determination of acidic herbicides in environmental waters. Anal Chem 67(9) 1637-1643... 

Jemal M., Xia Y., and Whigan D.B., 1998. The use of high-flow high performance liquid chromatography coupled with positive and negative ion electrospray tandem mass spectrometry for quantitative bioanalysis via direct injection of the plasma/serum samples. Rapid Commun Mass Spectrom 12 1389. 

Zeng H., Deng Y., and Wu J., 2003a. Fast analysis using monolithic columns coupled with high-flow online extraction and electrospray mass spectrometric detection for the direct and simultaneous quantitation of multiple components in plasma. J Chromatogr B 788 331. 

Bayliss and co-workers [10] combined ultra-high flow rates, parallel LC columns, a multiplex electrospray source, and mass spectrometric detection for the rapid determination of pharmaceuticals in plasma using four narrow bore (50 mm x 1 mm, 30 pm Oasis HLB) or capillary (50 mm x 0.18 mm, 25 pm Oasis HLB) HPLC columns with large particle sizes (to avoid high system back-pressure) in parallel with a multiple probe injector and a MUX MS interface. Small sample aliquots were injected directly into the system without sample pre-treatment procedure, obtaining very low limits of quantification (from 1 to 5 ng/mL). 

Bayliss M. Little D. Mallett D. Plumb R. Parallel ultra-high flow rate liquid chromatography with mass spectrometric detection using a multiplex electrospray source for direct, sensitive determination of pharmaceuticals in plasma at extremely high-throughput. Rapid Communications in Mass Spectrometry, 2000, 14, 2039-2045. 

Column size is another important consideration. For equipment designed for most routine laboratory HPLC situations the relative sensitivity of APTelectrospray instruments is better at low flow rates (0.2-0.8 mL/min) whereas the relative sensitivity of APCI instruments is enhanced at high flow rates (0.5-2 mL/min). As a result, small columns are appropriate for API-electrospray/MS and, if only one or two compounds of interest are found in a particular sample, high-resolution separations are not necessary. For APTelectrospray analysis of complex samples, 150 mm x 4.1 mml.D., 3 pm columns (flow 0.5-1.0 mL/min) are usually sufficient. For drug quantification involving analysis of single or low numbers of compounds, small columns such as 30 mm x 2.1 mm I.D., 3.5 pm columns (flow rate 0.2-0.4 mL/min) provide sufficient separation and a saving in both column cost and solvent utilization. The reduced injection volume required for the small columns often results in better resolution and increased sensitivity. 

If nonvolatile buffers cannot be completely avoided, their concentration should be kept at a minimum. High flow rates (due to a strong EOF) prevent rapid crystallization at the tip. Modern off-axis electrospray arrangements (orthogonal or Z-spray) tend to be more tolerant to nonvolatiles than classical on-axis interfaces. 

McCooeye, M., and Mester, Z. (2006). Comparison of flow injection analysis electrospray mass spectrometry and tandem mass spectrometry and electrospray high-field asymmetric waveform ion mobility mass spectrometry and tandem mass spectrometry for the determination of underivatized amino acids. Rapid Commun. Mass Spectrom. 20 1801-1808. 

Molina, C., G. Durand, and D. Barceld (1995). Trace determination of herbicides in estuarine waters by liquid chromatography-high-flow pneumatically assisted electrospray mass spectrometry. J. Chromatogr. A, 712 113-122. 

Zeng, H. Deng, Y Wu, J.-T. Past Analysis Using Monolithic Columns Coupled with High-flow On-line Extraction and Electrospray Mass Spectrometric Detection for the Direct and Simultaneous Quantitation of Multiple Components in Plasma, J. Chromatogr, B 788,331-337 (2003). 

Jemal, M. Qing, Y. Whigan, D.B. The Use of High-Flow High Performance Liquid Chromatography Coupled with Positive and Negative Ion Electrospray Tandem Mass Spectrometry for Quantitative Bioanalysis via Direct Injection of the Plasma/Serum Samples, Rapid Commun. Mass Spectrom. 12, 1389-1399 (1998). 

Bayliss, M.K. Little, D. Mallett, D.N. Plumb, R.S. Parallel Ultra-High Flow Rate Liquid Chromatography with Mass Spectrometric Detection Using aMulti-plex Electrospray Source for Direct, Sensitive Determination of Pharmaceuticals in Plasma at Extremely High Throughput, Rapid Commun. Mass Spectrom. 14, 2039-2045 (2000). 

Molina, C., Honing, M. and Barcelo, D. 1994. Determination of organophosphorus pesticides in water by solid-phase extraction followed by liquid chromato-graphy/high-flow pneumatically assisted electrospray mass spectrometry. Anal. Chem., 66 4444-4449. 

---