Influence of ionization source design on matrix effects during LC-ESI-MS/MS analysis.

Glycerophosphocholines (GPChos) are known to cause matrix ionization effects during the analysis of biological samples (i.e. plasma, urine, etc.) in LC-MS/MS. In general, such matrix effect is directly related to an insufficient sample clean-up of the biofluids. In addition to GPCho; design of ionization source and/or LC also plays a very important role in matrix effects. In this research paper, different types of matrix effects, i.e. ion suppression or enhancement were observed in differently designed ion sources coupled with different LCs, from the same molecule, acamprosate (ACM), under the same chromatographic conditions. ACM was analyzed in a negative polarity in electrospray ionization interface using Z-spray and orthogonal spray ion source design. The analyte showed almost complete ion suppression in the Z-spray ionization source coupled with UPLC/HPLC, whereas there was very little ion enhancement in the orthogonal spray ionization source coupled with HPLC. In both the cases different GPChos were responsible, as evident from the presence of m/z 815.4 in Z-spray ion source and m/z 759.0 in orthogonal spray ion source. Hence, this approach can be used to evaluate the matrix effects in plasma samples during development and validation of LC-MS/MS method of drugs and their metabolites in different biological matrixes.

Rapid and sensitive liquid chromatography/tandem mass spectrometry method for simultaneous determination of enalapril and its major metabolite enalaprilat, in human plasma: application to a bioequivalence study.

A rapid and most sensitive method for simultaneous determination of enalapril (ENP) and its metabolite, enalaprilat (ENPT), in human plasma using ESI-LC-MS/MS (electrospray ionization liquid chromatography tandem mass spectrometry) positive ion multiple reactions monitoring (MRM) mode, was developed and validated. The procedure involves a simple solid-phase extraction (SPE) followed by evaporation of the sample. Chromatographic separation was carried out on a Hypurity C(18) column (50 mm × 4.6 mm, 5 µm) with an isocratic mobile phase and a total run time of 2.0 min only. The MRM of ENP and ENPT is 377.10 → 234.20 and 349.20 → 206.10 respectively. The standard calibration curves showed excellent linearity within the range of 0.064 to 431.806 ng/mL for ENA and 0.064 to 431.720 ng/mL for ENPT (r ≥ 0.990). This is the only method which can quantitate upto 0.064 ng/mL for both ENP and ENPT in a single run with the shortest analysis time. In matrix effect experiment, this method shows a % CV (% coefficients of variation) of less than 5, which means that the proposed method is free from any kind of irregular ionization process. This method was successfully applied to a pharmacokinetic study after oral administration of enalapril maleate 20 mg tablet in Indian healthy male volunteers.

A LC-MS analysis of acamprosate from human plasma: pharmacokinetic application.

A rapid and highly sensitive method for the determination of acamprosate (ACM), in human plasma using ESI-LC-MS/MS (electrospray ionization liquid chromatography tandem mass spectrometry) in negative ionization polarity in multiple reactions monitoring (MRM) mode was developed and validated. The procedure involves a simple protein precipitation step. Chromatographic separation was carried out on a Hypersil BDS C(18) column (150 mm × 4.6 mm, 5 µm) with an isocratic mobile phase and a total run time of 2.5 min. The standard calibration curves were linear within the range of 7.04-702.20 ng/mL for ACM (r ≥ 0.990). This study briefly describes the role of ion source design on matrix effects. ACM shows matrix effects in z-spray ionization source design, whereas it has no matrix effects in orthogonal spray ion source design. This method was successfully applied to a pharmacokinetic study after oral administration of acamprosate 333 mg tablet in Indian healthy male volunteers.