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Sample diluent and mobile phase should be close in composition to provide good peak shape in RP systems. Is it still true for mixed mode separation?

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Sample diluent and mobile phase should be close in composition to provide good peak shape in RP systems. Is it still true for mixed mode separation?

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No. When two interactions are involved in retention of a compound, the mobile phase composition can be very different from mobile phase as long as at least one mode of separation is not disturbed. For example, when a positively charged molecule is retained on the Primesep 100 column, the sample diluent can have any amount of MeCN. The retention will be still non-disturbed due to the insignificant effect of organic concentration on electrostatic interaction. See example here.

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