Mathieu Lahaie

Algorithme Pharma, Laval, Quebec, Canada

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Publications (4)12.27 Total impact

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    ABSTRACT: RATIONALELiquid chromatography/tandem mass spectrometry (LC/MS/MS) instruments are selective and sensitive but can still be affected by isobaric interference or chemical noise arising from multiple sources such as the mobile phase. In this study, a high-performance liquid chromatography (HPLC) on-line mobile phase filtration setup is described and used to remove interference to allow better detection of the analyte of interest. METHODS For instance, a filtration device containing a chemical sorbent is installed at the HPLC outlet of the aqueous solvent pump A or the organic solvent pump B. This manuscript reports different case scenarios under reversed-phase and HILIC separations either in positive (ESI(+)) or negative electrospray ionization (ESI(–)) mode using selected reaction monitoring (SRM) scans as well as additional Q1 MS scans. RESULTSThe filtration of the aqueous effluent of the mobile phase using a porous graphitic carbon filter eliminated the isobaric interferences and improved the detectability of gestodene and perindopril-D4. Also, a strong cation-exchange guard column installed at the acetonitrile outlet pump was found helpful on reducing the baseline intensity and improving significantly the signal-to-noise ratio (S/N) of methenamine. Moreover, the on-line mobile phase filtration was efficient at removing chemical background ions in full scan mode. CONCLUSIONS This strategy demonstrated its usefulness by removing co-eluting isobaric interference, and reducing chemical background ions from the mobile phase, while drastically improving S/N. Copyright © 2014 John Wiley & Sons, Ltd.
    Rapid Communications in Mass Spectrometry 04/2014; 28(8). · 2.51 Impact Factor
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    ABSTRACT: Reanalysis of incurred samples showed that the bioanalytical method for the quantification of ramipril and ramiprilat was generating irreproducible results for ramiprilat. An additional peak interfering with ramiprilat was observed in the incurred samples but not in the calibrant and quality control samples. A similar interference was detected for ramipril, but it was chromatographically separated. Interferences were produced during sample preparation, which involves strong cation exchanger cartridges. The interfering products corresponded to the methylation of ramipril and ramiprilat glucuronide. Following this discovery, a reproducible method was developed and successfully validated for ramipril and ramiprilat. Additional stability tests were performed in the presence of glucuronide and diketopiperazine metabolites of ramipril and ramiprilat to demonstrate the method specificity.
    Bioanalysis 05/2011; 3(9):951-65. · 3.25 Impact Factor
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    ABSTRACT: The objective is to find elution conditions using different solid-phase extraction chemistries to reduce the amount of phospholipids in plasma extract, which is associated with matrix effect in LC-MS. Phospholipids' recovery was reduced by decreasing the eluents' methanol content applied to silica-based and polymer-based reversed-phase solid-phase extraction cartridges while 100% acetonitrile applied to the silica-based cartridges drastically minimized the phospholipids' elution. Silanol interactions are involved in the increased retention of phospholipids with silica-based reversed-phase cartridges when using high percentages of ACN in eluents. The bioanalytical usefulness of these findings was confirmed by successful extraction recovery of pharmaceutical compounds. Combinations of specific eluents and reversed-phase solid-phase extraction cartridges were found to prevent matrix effect due to phospholipids.
    Bioanalysis 06/2010; 2(6):1011-21. · 3.25 Impact Factor
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    ABSTRACT: In this study, the postcolumn addition approach was used to evaluate the impact of high pH modifiers on the sensitivity of 25 compounds by LC-MS/MS under positive ESI (ESI+). None of the compounds were significantly suppressed by the use of high pH modifiers. Most of them showed a signal enhancement by at least twofold compared with acidic modifiers. The sensitivity gained under high pH mobile phase was used to develop a bioassay for the quantification of candesartan. The use of high pH mobile phase allowed for fast sample preparation that would have been impossible under typical low pH chromatography. We have shown that high pH modifiers are sufficient to induce a signal enhancement for the majority of compounds detected under LC-ESI+-MS/MS.
    Bioanalysis 11/2009; 1(8):1419-30. · 3.25 Impact Factor