“…In such cases, it is necessary to use the negative ionization or switch to another type of ionization. If analyte derivatization has been employed to increase the ionization efficiency like for example with steroids or with paracetamol glucuronide (Ohta, Kawakami et al 2003), then the negative ionization mode may be even superior in sensitivity to the positive mode because the noise in negative mode may be lower, thereby increasing the signal/noise ratio (Higashi and Shimada 2004). Atmospheric pressure chemical ionization (APCI) interface may sometimes be beneficial over the ESI if the principally lower sensitivity of APCI is still adequate for the intended study.…”