That is really a good example for Triple Quadrupole LC-MS.Poor response at Positive ESI (+) mode, however, acceptable response at Negative ESI (-) mode.
Here, let's us assume that Tandem LC-MS instrument is under 100% perfect tuning mode ( just want to exclude the uncertainty of the Tandem LC-MS, just want to discuss about the nature of analyte in LC-MS)
General the Mass Response depends on the stability of molecular ion. -> look at the structure of p-Chlorophenol -> Positive ESI (+) mode, would very unstable due to the -Cl element (Cl element is EWG, that is to say, -Cl belongs electron withdrawing group. However, under Negative ESI (-) mode, the molecular ion would be more stable due to the present of Cl element. ( When this center is an electron rich carbanion or an alkoxide anion the presence of the Cl has a stabilizing effect.) that is the delocalization effect in the physical chem.
That is the reason why I always ask for the pKa value of each analyte @ Tech. For me, I NEVER under estimate the importance of pKa value.
So we always could change pH value to alter the disassociation of analyte in ESI mode. ( With ESI, convert the molecular ion from liquid phase into gas phase, enable the analyte evaporate into ion status -> obtain a decent response).
From the pKa, we know about the nature of analyte: basic,acid or neutral.
Then for basic analyte -> add some Acetic Acid/ Formic Acid ( pH ≈ pKa－2 ) -> enable the analyte generate positive (+) ion in solution for Positive ESI (+) mode. or for acid analyte -> add some ammonium to increase the pH ≈ pKa＋2 -> analyte is molecular ion with negative (-) for Negative ESI (-) mode.
Next time, will update my Tech Notebook about how to trouble-shooting the Poor Response of the Analyte based on the API 3200 Tandem QQQ LC-MS . (that is a golden treasure I learnd from Tech, U definetely need to buy me a drink for that)
