Journal des techniques de chromatographie et de séparation
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Influence of Ionization and Sample Processing Techniques on Matrix Effect of a Pulmonary Artery Antihypertensive Drug

Al Asmari AK, Ullah Z, Al Rawi AS, Ahmad I, Al Eid AS and Al Nowaiser NA

The issue of selectivity due to ion suppression or enhancement caused by the sample matrix has become a challenge in mass spectrometric (MS) analysis. It has been pragmatic that an efficient sample preparation method can reduce the matrix effect significantly. The study was planned to assess the effect of ionization type and sample preparation techniques on the presence or absence of matrix effect in quantitative liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis of bosentan (BSN) by post extraction addition method. Different sample processing techniques, i.e., protein precipitation (PPT), liquid–liquid extraction (LLE), and solid phase extraction (SPE) were evaluated. The sample were analyzed by both LC-electrospray ionization (ESI)-MS/MS and LCatmospheric pressure chemical ionization (APCI)-MS/MS. Chromatographic partition achieved on an Aquasil C18 column (100 × 2.1 mm, five μm). The mobile phase consisted of ammonium formate (pH 4.5) and methanol (10:90 v/v) in non-gradient elution mode. Our results demonstrated that both ionization sources showed matrix effect, but ESI was more prone to matrix effect than APCI. Sample processing techniques could decrease or increase matrix effect. PPT was found to be least efficient sample preparation technique, due to the presence of many remaining matrix constituents and often resulting in significant matrix effects. LLE also provided clean final extracts. However, the efficiency of LLE was lower than SPE. SPE methods resulted in cleaner extracts and considerably reduced the levels of residual matrix components from plasma samples that ultimately leads to significant reduction in matrix effects. LC-APCI-MS/MS was found to be the ionization of choice for quantitative analysis of BSN and other drugs with similar physicochemical properties. The combination of SPE and the ionization source offer a major advantage in reducing matrix effects resulting from plasma components and in improving the selectivity and sensitivity of drug analysis.