Carboxylic acids, neutral loss scan

Figure 3. Neutral loss scan detection of carboxylic acids in a mixture using NCI MS/MS. Upper scan is the normal NCI MS of the mixture. The lower, neutral loss scan shows significant responses only for carboxylic acids.

For the neutral loss scan, the first mass analyzer (Qj) scans all the masses (Figure 7(d)). The second mass analyzer (Q3) also scans, but at a fixed offset from the first mass analyzer. This offset corresponds to a neutral loss that is commonly observed for a particular class of compounds for example, the loss of 44 u (C02) from [M — H] ions will be indicative of carboxylic acids. Alkyl loss (C H2b+i) will be seen in the loss of 15, 29, or 43, etc. and the loss of 18 u (H20) will be indicative of a primary alcohol. A comprehensive table of common neutral fragments may be found in McLafferty and Turecek.32 The mass spectrum is then a record of all precursor ions that lose the specified neutral fragment. Again, neutral loss scans cannot be performed with trap-type MS instruments or with ToF analyzers. However, postacquisition analysis software can be used to search for the specified neutral loss. 

Constant neutral loss scan. Ql and Q3 are both scanning, but the voltage applied to Q3 is offset by an amount representing loss of a neutral molecule. For example, if one scanned Q3 with an offset of 44 u (CO2) then the scan from Ql would show carboxylic acids present in the sample. 

In a constant-neutral-loss scan, all precursors that undergo the loss of a specified common neutral are monitored. To obtain this information, both mass analyzers are scanned simultaneously, but with a mass offset that correlates with the mass of the specified neutral. Similar to the precursor-ion scan, this technique is also useful in the selective identification of closely related class of compounds in a mixture. For example, the loss of 44 Da is a common reaction of carboxylic acids. Through the constant-neutral loss scan, the identity of all carboxylic acids present in a complex mixture can be revealed. Similarly, by monitoring the 98-Da neutral loss, the presence of phosphopeptides can be detected in a complex mixture [6]. 

Q1 scanned, Q3 scanned. Both Q1 and Q3 are scanned at the same rate, but the scans are offset from each other by an mJz value corresponding to a specific, selected, component that is lost as a neutral species during the CID process in the collision cell (q2). When a particular neutral loss is known to occur in a class of compounds, this type of MS/MS analysis will identify the components of mixtures that release the neutral fragment e.g., carboxylic acids tend to lose CO2, and so the Q1 and Q3 scans are offset by 44 Da. 

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