How best do I degas my mobile phase

Noisy or drifting baselines and pressure fluctuations are signs of insufficient degassing. You should degas your mobile phase or improve your degassing procedure. 

Methanol/water as eluent Acetonitrile/water as eluent 

Acetonitrile/water and methanol/water mixtures are the most common mobile phase compositions in reversed-phase HPLC. Is there a preference Which is better acetonitrile or methanol  

Naturally, there is no general answer to this question. Selectivity differences could play a vital role for your separation. For example, some solutes can form methanolates, while acetonitrile stabilizes octahedral Cu, Cd and Zn complexes. Some general differences between the two solvents are listed below  

Acetonitrile is a better solvating agent More chemically different from water than methanol More toxic than methanol 

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