ionizing gas surrounding the interface and the mobile phase solvent are subject to chemical ionization at the ion source. Later, these ions react with the analyte and transfer their charge. The sample ions then pass through small orifice skimmers by means of or ion-focusing lenses. Once inside the high vacuum region, the ions are subject to mass analysis. This interface can be operated in positive and negative charge modes and singly-charged ions are mainly produced. APCI ion source can also handle flow rates between 500 and 2000 μl/min and it can be directly connected to conventional 4.6 mm ID columns. Atmospheric pressure photoionization (APPI) The APPI interface for LC-MS was developed simultaneously by Bruins and Syage in 2000. APPI is another LC-MS ion source/ interface for the analysis of neutral compounds that cannot be ionized using ESI. This interface is similar to the APCI ion source, but instead of a corona discharge, the ionization occurs by using photons coming from a discharge lamp. In the direct-APPI mode, singly charged analyte molecular ions are formed by absorption of a photon and ejection of an electron. In the dopant-APPI mode, an easily ionizable compound (Dopant) is added to the mobile phase or the nebulizing gas to promote a reaction of charge-exchange between the dopant molecular ion and the analyte. The ionized sample is later transferred to the mass analyzer at high vacuum as it passes through small orifice skimmers. Applications The coupling of MS with LC systems is attractive because liquid chromatography can separate delicate and complex natural mixtures, which chemical composition needs to be well established (e.g., biological fluids, environmental samples, and drugs). Further, LC-MS has applications in volatile explosive residue analysis. Nowadays, LC-MS has become one of the most widely used chemical analysis techniques because more than 85% of natural chemical compounds are polar and thermally labile and GC-MS cannot process these samples. As an example, HPLC-MS is regarded as the leading analytical technique for proteomics and pharmaceutical laboratories. Other important applications of LC-MS include the analysis of food, pesticides, and plant phenols. Pharmacokinetics LC-MS is widely used in the field of bioanalysis and is specially involved in pharmacokinetic studies of pharmaceuticals. Pharmacokinetic studies are needed to determine how quickly a drug will be cleared from the body organs and the hepatic blood flow. MS analyzers are useful in these studies because of their shorter analysis time, and higher sensitivity