This invention comprises an apparatus and method for generating sample ions from sample molecules in which a mixture of a sample and a matrix are vaporized by a laser beam and subsequently ionized by reagent corona ions. The decoupling of the vaporization and ionization steps allows each process to be separately optimized. The vaporization and ionization steps can be done in a sub-atmospheric pressure region. Alternatively, the vaporization and ionization steps can be done in a higher pressure region. In addition, the reagent corona ions can be generated in a vacuum chamber or a chamber at atmospheric pressure. Alternatively, the reagent ions can be generated in a sub-atmospheric region while the laser desorption occurs in an atmospheric region.