Development and validation of a hydrophilic interaction liquid chromatography–tandem mass spectrometric method for the analysis of paroxetine in human plasma

Abstract

A sensitive, simple, fast and rugged hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method for the determination of paroxetine was developed and validated over curve range 0.050-50 ng/mL using only 0.4 mL plasma. This is the first published LC-MS/MS method and the low limit of quantitation of this method is 10-fold lower than previously published methods. A simple liquid-liquid extraction method using methyl-tert butyl ether (MTBE) as the extraction solvent was used to extract paroxetine and the internal standard (IS) fentanyl-d(5) from plasma. The extract was evaporated to dryness, reconstituted and injected onto a silica column using a low aqueous-high organic mobile phase. The chromatographic run time was 2.0 min per injection, with retention times of 1.1 and 1.2 min for paroxetine and IS, respectively. The detection was by monitoring paroxetine at m/z 330 --> 192 and IS at m/z 342 --> 188, respectively. The inter-day precision and accuracy of the quality control (QC) samples were <5.0% relative standard deviation (RSD) and <2.9% relative error (RE). This method can be used for supporting therapeutical drug monitoring and pharmacokinetic or drug-drug interaction studies.

Use of liquid chromatography-tandem mass spectrometry for the analysis of pentoxifylline and lisofylline in plasma

“…Analysis by LC-MS-MS generally exhibits sensitivity in the range of 10 −6 -10 −12 g/mL plasma (Xia et al, 1999;Zhu et al, 2002;Phillips et al, 2001). The utility of LC-MS-MS has been demonstrated in the analysis of many classes of drugs including antibiotics (Ballesteros et al, 2003), antidepressants (Naidong and Eerkes, 2004), and hypoglycemics (Lin et al, 2004).…”

Determination of Paroxetine in Pharmaceutical Preparations Using HPLC with Electrochemical Detection

“…The precision was determined as the CV (%) of the results. Intraday precision was: 0.259; 0.144 and 0.119% (respectively), whereas interday precision was: The method was more precise than in other previously published papers [5,6,7,9,10,11,12,[15][16][17]. …”

“…The benefit of such kind of compound is that the interference from similar group is nullified, which assures the selectivity of the method. Then the methodology show higher specificity than previous works based on HPLC coupled to UV-Visible [5,6,15,17], fluorescence [7,9,12,16] or MS detectors [10,11]. In order to select the optimum oxidation potential for paroxetine, hydrodynamic voltammogram was plotted (Fig.…”

“…Several methods have been developed for the determination of paroxetine in plasma, including HPLC with ultraviolet [5,6], fluorescence (without or with derivatization using dansylchloride) [7][8][9], mass spectroscopy (MS) [10,11], diode array detection [12,13], or gas chromatography with MS detection [14,15] and applied therapeutic drug level monitoring. Only few methods have been published for the simultaneous determination of paroxetine and its metabolites in plasma, using HPLC with UV [2,16]; or applied to pharmacokinetic, therapeutic drug level monitoring, toxicological screening or forensic cases [17].…”

Critical Review of Development, Validation, and Transfer for High Throughput Bioanalytical LC-MS/MS Methods

“…LC-MS/MS using HILIC on silica column has been extensively studied and reviewed [68][69][70][71][72][73][74]. Because of the higher organic content in the mobile phase and the more favorable solution chemistry for ionization (acidic mobile phase for basic compounds and neutral mobile phase for acidic compounds), sensitivity improvement was observed [75]. Besides the feature of direct injection of SPE and LLE extracts, silica column has very low back pressure under HILIC condition, which facilitates high flow rate chromatography [76].…”