Challenges in optimizing sample preparation and LC‐MS/MS conditions for the analysis of carglumic acid, an N‐acetyl glutamate derivative in human plasma

Sharma, Primal; Shah, Priyanka A.; Sanyal, Mallika; Shrivastav, Pranav S.

doi:10.1002/dta.1774

Cited by 3 publications

(3 citation statements)

References 11 publications

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“…Method validation was performed following the US Food and Drug Administration () guidelines and the procedures were similar to those in our previous work (Shah & Shrivastav, ; Sharma, Shah, Sanyal, & Shrivastav, ; see Supporting Information).…”

Section: Methodsmentioning

confidence: 99%

Overcoming interference of plasma phospholipids using HybridSPE for the determination of trimetazidine by UPLC–MS/MS

Vanol

Yadav

Sanyal

et al. 2017

Biomedical Chromatography

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An improved, precise and reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the quantification of trimetazidine, using trimetazidine-d8 as the internal standard (IS). Interference owing to plasma phospholipids during sample preparation was overcome using a hybrid solid-phase extraction-phospholipid ultra cartridge. The mean extraction recovery of trimetazidine (98.66%) and trimetazidine-d8 (97.63%) from spiked plasma was consistent and reproducible. Chromatographic analysis was performed on a UPLC Ethylene Bridged Hybrid (BEH) C18 (50 × 2.1 mm, 1.7 μm) column with isocratic elution using acetonitrile-5 mm ammonium formate, pH 3.5 (40:60, v/v) as the mobile phase. The parent → product ion transitions for trimetazidine (m/z 267.1 → 181.1) and trimetazidine-d8 (m/z 275.2 → 181.1) were monitored on a triple quadrupole mass spectrometer with electrospray ionization functioning in the positive multiple reaction monitoring mode. The linearity of the method was established in the concentration range of 0.05-100 ng/mL for trimetazidine. The intra-batch and inter-batch accuracy and precision (CV) were 97.3-103.1 and 1.7-5.3%, respectively. Qualitative and quantitative assessment of matrix effect showed no interference of endogenous/exogenous components. The developed method was used to measure plasma trimetazidine concentration for a bioequivalence study with 12 healthy subjects.

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Section: Methodsmentioning

confidence: 99%

Overcoming interference of plasma phospholipids using HybridSPE for the determination of trimetazidine by UPLC–MS/MS

Vanol

Yadav

Sanyal

et al. 2017

Biomedical Chromatography

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“…However, the peak concentration of NCG in plasma after oral administration of 100 mg/kg body weight in a healthy male is only about 0.015 mM [56]. It is still a mystery how NCG is taken up and concentrated within liver mitochondria to reach millimolar concentrations.…”

Section: Discussionmentioning

confidence: 99%

Precision medicine in rare disease: Mechanisms of disparate effects of N -carbamyl- l -glutamate on mutant CPS1 enzymes

Shi

Zhao

Mew

et al. 2017

Molecular Genetics and Metabolism

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This study documents the disparate therapeutic effect of N-carbamyl-L-glutamate (NCG) in the activation of two different disease-causing mutants of carbamyl phosphate synthetase 1 (CPS1). We investigated the effects of NCG on purified recombinant wild-type (WT) mouse CPS1 and its human corresponding E1034G (increased ureagenesis on NCG) and M792I (decreased ureagenesis on NCG) mutants. NCG activates WT CPS1 sub-optimally compared to NAG. Similar to NAG, NCG, in combination with MgATP, stabilizes the enzyme, but competes with NAG binding to the enzyme. NCG supplementation activates available E1034G mutant CPS1 molecules not bound to NAG enhancing ureagenesis. Conversely, NCG competes with NAG binding to the scarce M792I mutant enzyme further decreasing residual ureagenesis. These results correlate with the respective patient’s response to NCG. Particular caution should be taken in the administration of NCG to patients with hyperammonemia before their molecular bases of their urea cycle disorders is known.

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“…The method validation was performed as per the USFDA guidelines [24] and was similar to our previous work [25] . The detailed procedures and their acceptance criteria are summarized in Supplementary material .…”

Section: Methodsmentioning

confidence: 99%

Sensitive and rapid determination of amantadine without derivatization in human plasma by LC–MS/MS for a bioequivalence study

Bhadoriya¹,

Rathnam²,

Dasandi³

et al. 2018

Journal of Pharmaceutical Analysis

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A highly sensitive, rapid and rugged liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for reliable estimation of amantadine (AMD), an antiviral drug in human plasma. The analyte and internal standard (IS), amantadine-d6 (AMD-d6), were extracted from 200 µL plasma by solid phase extraction on Phenomenex Strata-X-C 33 µ cartridges. Chromatography was performed on Synergi™ Hydro-RP C18 (150 mm × 4.6 mm, 4 µm) analytical column using a mixture of acetonitrile and 10 mM ammonium formate, pH 3.0 (80:20, v/v) as the mobile phase. Detection and quantitation was done by multiple reaction monitoring in the positive ionization mode for AMD (m/z 152.1 → 135.1) and IS (m/z 158.0 → 141.1) on a triple quadrupole mass spectrometer. The assay was linear in the concentration range of 0.50–500 ng/mL with correlation coefficient (r2) ≥ 0.9969. The limit of detection of the method was 0.18 ng/mL. The intra-batch and inter-batch precisions were ≤ 5.42% and the accuracy varied from 98.47% to 105.72%. The extraction recovery of amantadine was precise and quantitative in the range of 97.89%–100.28%. IS-normalized matrix factors for amantadine varied from 0.981 to 1.012. The stability of AMD in whole blood and plasma was evaluated under different conditions. The developed method was successfully applied for a bioequivalence study with 100 mg of AMD in 32 healthy volunteers. The reproducibility of the assay was determined by reanalysis of 134 subject samples.

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Challenges in optimizing sample preparation and LC‐MS/MS conditions for the analysis of carglumic acid, an N‐acetyl glutamate derivative in human plasma

Cited by 3 publications

References 11 publications

Overcoming interference of plasma phospholipids using HybridSPE for the determination of trimetazidine by UPLC–MS/MS

Overcoming interference of plasma phospholipids using HybridSPE for the determination of trimetazidine by UPLC–MS/MS

Precision medicine in rare disease: Mechanisms of disparate effects of N -carbamyl- l -glutamate on mutant CPS1 enzymes

Sensitive and rapid determination of amantadine without derivatization in human plasma by LC–MS/MS for a bioequivalence study

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