• Mass Spectrometry Letters
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• v.11 no.4
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• pp.71-76
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• 2020

While montelukast (ML), a cysteinyl-leukotriene type 1 receptor (CysLT1) antagonist is widely used to treat symptoms of rhinitis or asthma, its formulations are mainly limited to solid preparation due to its instability. Recently, there have been attempts to develop various ML dosage forms, and this situation increases the demand of sensitive and creditable methods to determine ML in various samples such as plasma. Thus, here, a simple and efficient method to determine ML in rat plasma using liquid-liquid extraction (LLE) and multiple reaction monitoring was presented. The mixture of DCM:EtOAc (25:75, v/v), the optimized extract solvent for LLE was found to be effective to extract ML without hydrophilic salts and proteins from the sample with limited volume. Also, the use of zafirlukast, instead of expensive ML-d6, as the internal standard makes the present method economical. The developed method was successfully validated in terms of selectivity, matrix effects (-14.8--6.9%), linearity (r230.998 within 0.5-500 ng/mL), sensitivity (the limit of detection and the lower limit of quantitation, ≤0.5 ng/mL), accuracy (88.4-100.6%), precision (3.0-13.3%), and recovery (80.8-86.3%) by following the FDA guidelines. Finally, the applicability of the validated method to pharmacokinetics (PK) studies was confirmed by the successful determination of PK parameters through it following oral administration of Singulair® granule in rats. Therefore, the present method can contribute to the development of new ML formulations through its performance to determine ML in rat plasma efficiently and sensitively.

• Food Engineering Progress
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• v.22 no.4
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• pp.295-303
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• 2018

Polyphenol profiles, physicochemical properties, antioxidant activities, and inhibitory effect of adipocyte differentiation of Houttuynia cordata fermented with Lactobacillus brevis B84 were evaluated. Six polyphenols were characterized for this plant by using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and the results were compared with total phenolic content by a spectrophotometric method. The total amount of the identified polyphenols was lower than that determined by the spectrophotometric method. However, the fermentation process influenced polyphenol composition such as content of vanillic acid and caffeic acid. The phytochemical profiles were evaluated by high-performance liquid chromatography with UV and electrospray ionization mass spectrometry detection ($HPLC-DAD-ESI-MS^n$). Total sugar and reducing sugar contents decreased after fermentation. Antioxidant activities such as DPPH, ABTS, and superoxide anion radical scavenging and reducing power were evaluated to compare the beneficial effect after fermentation. Fermented H. cordata increased the lipolytic effect in 3T3-L1 adipocytes. Overall, the results indicate that the fermentation of H. cordata with L. brevis B84 produces changes of phenolic compounds, antioxidant activity, and lipolytic effect.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.223.2-223.2
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• 2003

A rapid, sensitive and selective liquid chromatography-tandem mass spectrometric (LC/MS/MS) method for the determination of eupatilin in human plasma was developed. Eupatilin and internal standard, (S)-[N-3-(4-(2-(1-methyl-5-tetrazolyl)-pyridine-5-y1)- 3-fluorophenyl)-2-oxo-5-oxazolidinyl]methyl acetamide (DA-7867) were extracted from human plasma by liquid-liquid extraction and analyzed on a phenyl-hexyl column with the mobile phase of acetonitrile-ammonium formate (10 mM, pH 3.0) (60:40, v/v). (omitted)

• Mass Spectrometry Letters
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• v.10 no.1
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• pp.38-42
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• 2019

Damaurone D belongs to the genus Rosa and is a traditional medicinal product used for the treatment of depression, inflammation, and infectious diseases. The purpose of this study was to develop a simple liquid chromatography-tandem mass spectrometry method for the detection of damaurone D in rat plasma and to demonstrate its application in pharmacokinetic studies. Damaurone D and berberine (internal standard) were extracted with acetonitrile using a protein precipitation method. Mass transition was monitored in multiple reaction monitoring mode at m/z $323.2{\rightarrow}267.0$ for damaurone D and m/z $336.1{\rightarrow}320.0$ for berberine in positive ion mode. Analytical validation was conducted by evaluating the specificity, linearity, accuracy, precision, matrix effect, extraction recovery, and stability. The calibration curves were linear over 2-1000 ng/mL. The intra- and inter-day precision and accuracy of quality control samples were 4.79-13.33% and 86.23-102.75%, respectively. The matrix effect and extraction recovery were 96.11-98.47% and 96.11-102.25%, respectively. In the pharmacokinetic study after intravenous administration of damaurone D at a dose of 3 mg/kg in rats, the area under the curve and clearance of damaurone D in rat plasma were $16750.26{\pm}2676.10min{\cdot}ng/mL$ and $182.44{\pm}31.36mL/min/kg$, respectively.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.539-549
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• 2019

Background: 20(S)-Protopanaxadiol (PPD), the aglycone part of 20(S)-protopanaxadiol ginsenosides, possesses antidepressant activity among many other pharmacological activities. It is currently undergoing clinical trial in China as an antidepressant. Methods: In this study, an ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass tandem mass spectrometry method was established to identify the metabolites of PPD in human plasma and urine following oral administration in phase IIa clinical trial. Results: A total of 40 metabolites in human plasma and urine were identified using this method. Four metabolites identified were isolated from rat feces, and two of them were analyzed by NMR to elucidate the exact structures. The structures of isolated compounds were confirmed as (20S,24S)-epoxydammarane-12,23,25-triol-3-one and (20S,24S)-epoxydammarane-3,12,23,25-tetrol. Both compounds were found as metabolites in human for the first time. Upon comparing our findings with the findings of the in vitro study of PPD metabolism in human liver microsomes and human hepatocytes, metabolites with m/z 475.3783 and phase II metabolites were not found in our study whereas metabolites with m/z 505.3530, 523.3641, and 525.3788 were exclusively detected in our experiments. Conclusion: The metabolites identified using ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry in our study were mostly hydroxylated metabolites. This indicated that PPD was metabolized in human body mainly through phase I hepatic metabolism. The main metabolites are in 20,24-oxide form with multiple hydroxylation sites. Finally, the metabolic pathways of PPD in vivo (human) were proposed based on structural analysis.

• Nuclear Engineering and Technology
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• v.54 no.12
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• pp.4636-4643
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• 2022

A time-of-flight and energy (TOF-E) detection system for the measurement of ²³⁶U accelerator mass spectrometry (AMS) has been developed to improve the ²³⁶U/²³⁸U sensitivity at Micro Analysis Laboratory, Tandem accelerator (MALT), The University of Tokyo. With observing TOF distribution of ²³⁵U, ²³⁶U and ²³⁸U, this TOF-E detection system has clearly separated ²³⁶U from the interference of ²³⁵U and ²³⁸U when measuring three kinds of uranium standards. In addition, we have developed a novel method combining kernel-based density estimation method and multi-Gaussian fitting method to estimate the ²³⁶U/²³⁸U sensitivity of the TOF-E detection system. Using this new estimation method, 3.4 × 10^-12 of ²³⁶U/²³⁸U sensitivity and 1.9 ns of time resolution are obtained. ²³⁶U/²³⁸U sensitivity of TOF-E detection system has improved two orders of magnitude better than that of previous gas ionization chamber. Moreover, unknown species other than uranium isotopes were also observed in the measurement of a surface soil sample, which has demonstrated that TOF-E detection system has a higher sensitivity in particle identification. With its high sensibility in mass determination, this TOF-E detection system could also be used in other heavy isotope AMS.

• Mass Spectrometry Letters
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• v.12 no.4
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• pp.200-205
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• 2021

Polynemoraline C, a pyridocoumarin alkaloid, exhibits anticholinergic, anti-inflammatory, antitumor, and antimicrobial activities. A sensitive analytical method of polynemoraline C in mouse plasma was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Polynemoraline C and ¹³C-caffeine (internal standard) in mouse plasma were extracted using a liquid-liquid extraction method coupled with ethyl acetate. This extraction method resulted in high and reproducible extraction recovery in the range of 73.49%-77.31% with no interfering peaks around the peak retention time of polynemoraline C and ¹³C-caffeine. The standard calibration curves for polynemoraline C were linear over the range of 0.5-200 ng/mL with r² > 0.985. The accuracy, precision, and the stability of the data were within acceptable limits on the FDA guideline. After intravenous and oral administration of polynemoraline C at doses of 5 and 30 mg/kg, respectively, the present method was successfully applied to the pharmacokinetic study of polynemoraline C. Polynemoraline C in mouse plasma showed a multi-exponential elimination pattern with a high volume of distribution values. This compound's absolute oral bioavailability was found to be 17.0%. Polynemoraline C's newly developed LC-MS/MS method can be used for further studies on the efficacy, toxicity, and biopharmaceutics of polynemoraline C, as well as its pharmacokinetic studies.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.46 no.2
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• pp.154-159
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• 2013

The AOAC Mouse Bioassay method (MBA) has been widely used for routine monitoring of paralytic shellfish poisoning (PSP) for more than 50 years. However, this method has low sensitivity and experiences interference from other components in the extract. Also, ethical issues have been raised against the continued use of this live-mouse assay. To establish an alternative method for PSP analysis, we attempted to develop PSP analysis conditions using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The LC-MS/MS analysis of reference material showed very reasonable accuracy, and the analysis time was just 15 min. However, the recovery rate of toxin spike samples using the LC-MS/MS analysis was 59.4-91.0%. We also attempted to remove the matrix effect using shellfish extracts, but recoveries of C1 and C2 did not improve. A comparison between the results of MBA and LC-MS/MS analysis revealed good correlations, with values of 0.8878 and 0.9211 for oyster and mussel matrices, respectively.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.2
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• pp.98-100
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• 2015

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a rare mitochondrial fatty-acid oxidation disorder that is inherited as an autosomal recessive pattern. SCAD deficiency is caused by mutations in the ACADS gene (Acyl-CoA Dehydrogenase, Short-chain, OMIM #606885), which encodes SCAD, the mitochondrial enzyme that catalyzes the first reaction in the beta-oxidation of fatty acids four to six carbons in length. Here, we describe one Korean pediatric case of SCAD deficiency, which was diagnosed during newborn screening through tandem mass spectrometry. An increased concentration of butyrylcarnitine was detected on the newborn screening test, and the urine organic acid analysis showed increased urinary excretion of ethylmalonic acid. The patient has been asymptomatic and has shown normal growth and development by 8 months of age without any intervention during follow-up period.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.44 no.1
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• pp.45-49
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• 2011

As a first step toward identifying a new method for testing sea snail tissue for toxins, and thus prevent food poisoning due to the ingestion of contaminated snails, we measured the tetramine [$(CH_3)_4N^+$] contents of sea snails from the Korean coast using both liquid chromatography-tandem mass spectrometry (LC-MS/MS) and ion chromatography. For tetramine tested, good linearity ($r^2$ = 0.9996) was observed between the amounts in the injected samples and the peak areas of standard toxins, which ranged from 0.1 to 100 ng. The recovery (%) of tetramine from spiked tissue and mid-gut gland samples ranged from 84.0 to 95.3%. The quantitative results for tetramine using this method were in good agreement with the theoretical values. LC-MS/MS has both high sensitivity and selectivity, which makes it possible to measure trace quantities of tetramine in samples.