A simple and rapid determination of valproic acid in human plasma using a non‐porous silica column and liquid chromatography with tandem mass spectrometric detection

Matsuura, Keiichi; Ohmori, Tomofumi; Nakamura, Mitsuhiro; Itoh, Yoshinori; Hirano, Kazuyuki

doi:10.1002/bmc.944

Cited by 41 publications

(28 citation statements)

References 18 publications

(43 reference statements)

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“…In our method, the sample preparation is very simple and rapid and offers a shorter time of analyses and a lower cost in comparison with the other longer methods which used extraction prior to LC assays. Therefore, Matsuura et al [14] have determined VA from plasma by LC-MS/MS after SPE and they obtained an LLOQ of 0.5 μg/mL and a recovery of only 84%. Jain et al [13] have also reported an LC-MS/MS method using an SPE of VA prior to LC analysis with an LLOQ of 2 μg/mL and a good recovery of 99.73%.…”

Section: Resultsmentioning

confidence: 99%

“…Because VA is strongly bound to proteins, most methods involve primarily precipitation of proteins, followed by extraction of VA in organic solvents and derivatization. Generally, VA is isolated by liquid-liquid extraction (LLE) [8,9,11] or solid-phase extraction (SPE) [12][13][14] from acidic medium. Both extraction and derivatization are time-consuming steps, increase the cost of assay and can affect the recovery.…”

Section: Introductionmentioning

confidence: 99%

“…Sample preparation is more simple and rapid and often includes precipitation of proteins (PP) [15] and/or extraction [11][12][13][14] before chromatographic analysis.…”

Section: Introductionmentioning

confidence: 99%

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A New High-Throughput LC-MS/MS Assay for Therapeutic Level Monitoring of Valproic Acid in Human Plasma

Vlase¹,

Popa

Leucuţa³

2008

Sci. Pharm.

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A new high-throughput liquid chromatographic tandem mass spectrometric (LC-MS/MS) assay for the quantification of valproic acid in human plasma was developed and validated. The separation was performed on a Zorbax SB-C18 column under isocratic conditions using a 48:52 (v/v) mixture of acetonitrile and 0.1% (v/v) acetic acid in water at 45 °C with a flow rate of 0.8 mL/min. The detection of valproic acid was performed in SIM mode (m/z 143.1). The human plasma samples (0.2 mL) were deproteinized with methanol and aliquots of 2 μL from supernatants obtained after centrifugation were directly injected into the chromatographic system. The method shows a good linearity (r > 0.9972), precision (CV > 7.8 %) and accuracy (bias > 5.7 %) over the range of 5-200 μg/mL plasma. Lower limit of quantification (LLOQ) was 5 μg/mL and the recovery was between 98-106 %. The method is not expensive, it needs a minimum time for plasma sample preparation and has a run-time of 2.4 min for instrument analysis (retention time of valproic acid was 1.8 min). The developed and validated high-throughput method is very simple, rapid and efficient, with wide applications in clinical level monitoring, pharmacokinetics and bioequivalence studies. Keywords

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A New High-Throughput LC-MS/MS Assay for Therapeutic Level Monitoring of Valproic Acid in Human Plasma

Vlase¹,

Popa

Leucuţa³

2008

Sci. Pharm.

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“…Therefore, LC-MS 2 can be performed only by monitoring the deprotonated molecule (-ESI), such as in the case of valproic acid (VPA) (143→143) [10]. With further research, it could be demonstrated that analyte adduct formation/fragmentation may also be used for this problematic drug.…”

Section: Lc-msmentioning

confidence: 99%

LC–MS ⁿ Small-Molecule Drug Analysis in Human Serum: Could Adducts have Good Prospects for Therapeutic Applications?

Dziadosz

2018

Bioanalysis

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Analyte adduct formation is well known in LC-MS n [1,2]; however, in comparison to the most important means of ionization in ESI MS such as analyte protonation (positive ion mode) and deprotonation (negative ion mode), its application can be defined as rather limited. This is not really a surprise when considered that adduct formation was sidelined as a pitfall in LC-MS n analysis equivalent to other sources of inaccuracy [3,4]. Nevertheless, the latest research demonstrated that this strategy of analyte ionization/fragmentation is a promising alternative for solving different problems concerning the analysis of small molecules relevant in clinical/forensic toxicology, with possibilities exceeding standard applications focused on higher sensitivities in comparison to protonation/deprotonation often observed and used for quantitative analysis [5,6]. In this article, different strategies of LC-MS n analyses of problematic small-molecule drugs based on analyte adduct formation interesting for the field of bioanalysis were discussed on the basis of the latest literature. In focus are both small drugs with poor fragmentation, where the detection of small ion fragments is necessary when the conventional LC-MS 2 strategy is applied, and small drugs producing no stable ion fragments, where the product ion spectrum has no signals applicable for drug detection. Further, the application of analyte adducts in the LC-MS n analysis of small-molecule drugs with problematic ionization based on protonation/deprotonation was also pointed out. Generation of bigger ion fragments of small-molecule drugs with poor fragmentation for LC-MS2 applications To avoid the detection of small ion fragments, an analyte adduct formation/fragmentation strategy was developed for the generation of bigger ion fragments that could be used for LC-MS 2 analysis of γ-hydroxybutyrate (GHB), which was used as a model drug [7]. A GHB sodium acetate adduct ion was described as a target, of which the fragmentation was the basis for LC-MS 2 analysis to avoid the detection of ions smaller than 85 Da as described previous [8]. Sample preparation based on a protein precipitation performed with the mobile phase, together with a short analysis time of 3 min and a calculated LOD/LOQ of 1 μg/ml, directly warranted a fast and sensitive analysis. Under conditions used with a mobile phase consisting of 10% A (H 2 O/methanol = 95/5, vv) and 90% B (H 2 O/methanol = 9/97, vv) both with 10 mM ammonium acetate and 0.1% acetic acid corresponding adducts were identified for GHB-D6 applied as internal standard for appropriate signal compensation. Realization of LC-MS3 analyzes for small-molecule drugs with poor ion fragmentation The same mobile phase conditions were used to develop a protein precipitation based sample preparation for GHB analysis, with a three-stage m/z separation strategy that was applied for drug detection by LC-MS 3 . The application of the GHB sodium acetate adduct ion enabled the optimization of a two-step fragmentation (185→103→85), which resulted in an ...

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“…A smilar limitation has been reported regarding valproic acid, a small molecule antiepileptic agent, and its metabolite. [14][15][16][17][18][19] Thus, pseudo MRM would be a useful for determining small stable compounds producing no fragmented ions suitable for conventional MRM.…”

mentioning

confidence: 99%

Determination of Menadione by Liquid Chromatography-Tandem Mass Spectrometry Using Pseudo Multiple Reaction Monitoring

et al. 2017

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This study aimed to develop a menadione (MD) determination method employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a pseudo multiple reaction monitoring (MRM) technique, wherein two quadrupoles are used to monitor the same ion. Detection limits of 40 and 2 pg were obtained for MD and its deuterium-labeled form, respectively, whereas MD intra-and inter-assay coefficient of variation values were determined as 5.4 -8.2%, with the corresponding recoveries equaling 90.5 -109.6%. The developed method enables determination of MD in urine, plasma, cell extract, and culture media, demonstrating that pseudo multiple reaction monitoring can achieve quantification of compounds forming no suitable product ions, such as MD.

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A simple and rapid determination of valproic acid in human plasma using a non‐porous silica column and liquid chromatography with tandem mass spectrometric detection

Cited by 41 publications

References 18 publications

A New High-Throughput LC-MS/MS Assay for Therapeutic Level Monitoring of Valproic Acid in Human Plasma

A New High-Throughput LC-MS/MS Assay for Therapeutic Level Monitoring of Valproic Acid in Human Plasma

LC–MS ⁿ Small-Molecule Drug Analysis in Human Serum: Could Adducts have Good Prospects for Therapeutic Applications?

Determination of Menadione by Liquid Chromatography-Tandem Mass Spectrometry Using Pseudo Multiple Reaction Monitoring

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A simple and rapid determination of valproic acid in human plasma using a non‐porous silica column and liquid chromatography with tandem mass spectrometric detection

Cited by 41 publications

References 18 publications

A New High-Throughput LC-MS/MS Assay for Therapeutic Level Monitoring of Valproic Acid in Human Plasma

A New High-Throughput LC-MS/MS Assay for Therapeutic Level Monitoring of Valproic Acid in Human Plasma

LC–MS n Small-Molecule Drug Analysis in Human Serum: Could Adducts have Good Prospects for Therapeutic Applications?

Determination of Menadione by Liquid Chromatography-Tandem Mass Spectrometry Using Pseudo Multiple Reaction Monitoring

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LC–MS ⁿ Small-Molecule Drug Analysis in Human Serum: Could Adducts have Good Prospects for Therapeutic Applications?