To get the maximum sensitivity from LC-MS ,go for SIM mode, in this mode the detector response for the ion species is maximum, further on you can use CC for detection.Sensitivity also depends upon the detector used.
The maximum obtainable sensitivity using LC-MS also depends on the ionisation efficiency, meaning that the sensitivity is compound dependent. Therefore, a detection limit of 0.006 ppb (I guess this is what you mean) is not always possible to reach. If you are working with a triple quad system, I would opt for SRM mode which is more sensitive than SIM-mode.
Which kind of molecule?
Choose the most appropriate ionisation mode/probe.
One clue in ESI+ : consider post column addition of an acid at a low flow. I already experienced an increase by a factor one thousand for the detection of some peptides.
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