scholarly journals Chromatography-tandem MASS spectrometry (HPLC-MS/MS) for the detection of valproic acid and its metabolites in blood plasma

2018 ◽  
Vol 10 (2) ◽  
pp. 35-42
Author(s):  
A. S. Malygin ◽  
N. S. Popov ◽  
M. A. Demidova ◽  
M. N. Kudrayshova
Keyword(s):  
Valproic Acid ◽  
Blood Plasma ◽  
Ammonium Acetate ◽  
Therapy Monitoring ◽  
Multiple Reaction Monitoring ◽  
Negative Ion ◽  
The Individual ◽  
Negative Ion Mode ◽  
Patients With Epilepsy ◽  
In Blood Plasma

Aim: to adapt the HPLC-MS/MS technique to determining valproic acid and its metabolites in blood plasma for drug therapy monitoring.Materials and Methods: The chromatographic assay was run using an Agilent 1260 Infinity II chromatograph with a Phenomenex synergi Fusion analytical column 4 μm-C18 2×50 mm. The mobile phase consisted of 0.1% ammonium acetate in distilled water and 0.1% ammonium acetate in methanol (10:90 v/v, 0.5 ml/min). The multiple ions monitoring (MIM) mode was used for mass- spectrometric detection of valproic acid at m/z = 143.1, with the negative ion mode. The method  was found applicable over the range from 1 mcg/ml to 200 mcg/ml of valproic acid. For the mass  spectroscopy detection of valproic acid metabolites, the multiple reaction monitoring (MRM mode)  was used. MS identifications of 2-propyl-4-pentanoil-β-О-glucuronide; 2-propyl-4-pentenoic acid,  3-hydroxy-2- propylpentanoic acid, 4-hydroxy-2-propylpentanoic acid, 2-propylglutaric acid and 3- oxo-2-propylpentanoic acid in the negative ion mode were carried out at m/z 319.2→143.2; m/z  140.1→140.1; m/z 159.1→101; m/z 159.1→123.1; m/z 173→129.1 and m/z 157.05→11,  respectively. The method was sensitive over the range from 10 ng/ml to 500 ng/ml of the tested  compounds.Results: The developed technique allows for determining valproic acid and its metabolites in a single sample; thus, the preliminary stage of separate sample preparation can be omitted, which increases the informative value of the assay without increasing its cost.Conclusion: This innovative methodology for the quantification of valproic acid and its metabolites in the blood plasma is expected to facilitate the individual approach to the treatment of patients with epilepsy, thereby increasing the efficacy and safety of the pharmacotherapy.

scholarly journals Studies of the pharmacokinetics of morroniside and loganin in rat after oral administration of raw and wine-processed Corni fructus by UPLC-QqQ-MS/MS

2022 ◽  
Vol 20 (2) ◽  
pp. 411-418
Author(s):  
Wei Wang ◽  
Xuechun Wang ◽  
Qiang Zhang ◽  
Ru Jia ◽  
Chunjie Du ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Negative Ion ◽  
Pharmacokinetic Parameters ◽  
Tissue Samples ◽  
Multiple Reaction Monitoring Mode ◽  
The Mean ◽  
Corni Fructus ◽  
Negative Ion Mode

Purpose: To study the pharmacokinetics of morroniside (MR) and loganin (LG) in rats after oral administration of raw and wine-processed Corni fructus by UPLC-QqQ-MS/MS. Methods: Arctiin (AT) was used as internal standard, and the plasma or tissue samples were extracted twice using ethyl acetate. Electrospray ionization (ESI) negative ion mode was used, and the multiple reaction monitoring mode (MRM) was set in acquisition mode. The extraction and detection method is supported by selectivity, sensitivity, precision, accuracy, stability, extraction, recovery and matrix effect. The non-atrioventricular model of das2.0 software was used to calculate the pharmacokinetic parameters. Results: The absorption rate of MR (PTmax=0.092) and LG (PTmax=0.092) in Corni Fructus after wine-processing was faster in rats. The mean residence time was longer, and distribution of MR (PMRT0~t = 0.294) and LG (PMRT0~t = 0.000) in wine-processed Corni Fructus group increased in liver and kidneys. Conclusion: The proposed method has been successfully validated and is suitable for studying the pharmacokinetics of the two analytes in rats.

Rapid determination of patulin in medicinal hawthorn fruits by HPLC-MS/MS

2012 ◽  
Vol 5 (1) ◽  
pp. 31-36 ◽  
Author(s):  
L. Xiang ◽  
Y. Gao ◽  
D. Liu ◽  
M. Yang
Keyword(s):  
Rapid Determination ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Negative Ion ◽  
Liquid Liquid Extraction ◽  
Relative Standard ◽  
Limit Of Quantitation ◽  
Hawthorn Fruit ◽  
Negative Ion Mode

An HPLC-tandem mass spectrometry method was developed for the determination of patulin (PAT) in dried medicinal hawthorn fruit, a well-known traditional medicine in China. Liquid-liquid extraction was applied in the sample preparation. Multiple reaction monitoring was performed at m/z 153/109 for PAT and m/z 317/273 for internal standard zearalenone in the negative ion mode with electrospray ionisation source. Good linearity was achieved when spiked PAT concentrations were in the range of 10-500 μg/kg, with coefficient being 0.9993. The limit of quantitation was 10 μg/kg. The extraction recoveries for the spiked PAT at concentrations of 20, 100 and 400 μg/kg were 64.5%, 64.6% and 63.9%, respectively, with relative standard deviations of 1.25%, 2.82% and 2.61%. The intra-day and inter-day precision were in the range of 2.2-9.6% and 5.9-6.4%. This rapid, sensitive and reliable method was applied in 25 batches of medicinal hawthorn fruit, in which PAT was detected in 8 batches, including those that were baked or charred.

scholarly journals Simultaneous Quantification of Propylthiouracil and Its N-β-d Glucuronide by HPLC-MS/MS: Application to a Metabolic Study

2021 ◽  
Vol 14 (11) ◽  
pp. 1194
Author(s):  
Min Li ◽  
Qingfeng He ◽  
Li Yao ◽  
Xiaofeng Wang ◽  
Zhijia Tang ◽  
...  
Keyword(s):  
Pediatric Population ◽  
Multiple Reaction Monitoring ◽  
Negative Ion ◽  
Metabolic Study ◽  
Simultaneous Quantification ◽  
Mechanistic Investigation ◽  
Age Dependent ◽  
Carry Over ◽  
Negative Ion Mode

Propylthiouracil (PTU) is commonly prescribed for the management of hyperthyroidism and thyrotoxicosis. Although the exact mechanism of action is not fully understood, PTU is associated with hepatoxicity in pediatric population. Glucuronidation mediated by uridine 5′-diphospho-glucuronosyltransferases (UGTs), which possess age-dependent expression, has been proposed as an important metabolic pathway of PTU. To further examine the metabolism of PTU, a reliable HPLC-MS/MS method for the simultaneous quantification of PTU and its N-β-D glucuronide (PTU-GLU) was developed and validated. The chromatographic separation was achieved on a ZORBAX Extend-C18 column (2.1 × 50 mm, 1.8 μm) through gradient delivery of a mixture of formic acid, methanol and acetonitrile. The electrospray ionization (ESI) was operated in its negative ion mode while PTU and PTU-GLU were detected by multiple reaction monitoring (MRM). This analytical method displayed excellent linearity, sensitivity, accuracy, precision, recovery and stability while its matrix effect and carry-over were insignificant. Subsequently, the in vitro metabolism of PTU was assessed and UGT1A9 was identified as an important UGT isoform responsible for the glucuronidation of PTU. The information obtained from this study will facilitate future mechanistic investigation on the hepatoxicity of PTU and may optimize its clinical application.

scholarly journals LC-ESI/LTQ-Orbitrap-MS Based Metabolomics in Evaluation of Bitter Taste of Arbutus unedo Honey

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2765
Author(s):  
Paola Montoro ◽  
Gilda D’Urso ◽  
Adam Kowalczyk ◽  
Carlo Ignazio Giovanni Tuberoso
Keyword(s):  
High Resolution ◽  
Bitter Taste ◽  
Principal Component ◽  
Mediterranean Area ◽  
Negative Ion ◽  
Strawberry Tree ◽  
Electrospray Source ◽  
The Individual ◽  
Negative Ion Mode ◽  
Orbitrap Ms

Strawberry tree honey is a high-value honey from the Mediterranean area and it is characterised by a typical bitter taste. To possibly identify the secondary metabolites responsible for the bitter taste, the honey was fractionated on a C18 column and the individual fractions were subjected to sensory analysis and then analysed by liquid chromatography coupled with high-resolution tandem mass spectrometry in negative ion mode, using a mass spectrometer with an electrospray source coupled to a hybrid high resolution mass analyser (LC-ESI/LTQ-Orbitrap-MS). A chemometric model obtained by preliminary principal component analysis (PCA) of LC-ESI/LTQ-Orbitrap-MS data allowed the identification of the fractions that caused the perception of bitterness. Subsequently, a partial least squares (PLS) regression model was built. The studies carried out with multivariate analysis showed that unedone (2-(1,2-dihydroxypropyl)-4,4,8-trimethyl-1-oxaspiro [2.5] oct-7-en-6-one) can be considered responsible for the bitter taste of strawberry tree honey. Confirmation of the bitter taste of unedone was obtained by sensory evaluation of a pure standard, allowing it to be added to the list of natural compounds responsible for giving the sensation of bitterness to humans.

scholarly journals Metabolite Profiling and Characterization of LW6, a Novel HIF-1α Inhibitor, as an Antitumor Drug Candidate in Mice

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1951
Author(s):  
Kiho Lee ◽  
Ji-Yoon Lee ◽  
Kyeong Lee ◽  
Cho-Rock Jung ◽  
Min-Ju Kim ◽  
...  
Keyword(s):  
Ion Trap ◽  
Multiple Reaction Monitoring ◽  
Parent Compound ◽  
Hypoxia Inducible Factor ◽  
Metabolite Identification ◽  
Pharmacokinetic Profile ◽  
Negative Ion ◽  
Drug Candidate ◽  
Amide Hydrolysis ◽  
Negative Ion Mode

A novel HIF (hypoxia-inducible factor)-1α inhibitor, the (aryloxyacetylamino)benzoic acid derivative LW6, is an anticancer agent that inhibits the accumulation of HIF-1α. The aim of this study was to characterize and determine the structures of the metabolites of LW6 in ICR mice. Metabolite identification was performed using a predictive multiple reaction monitoring-information dependent acquisition-enhanced product ion (pMRM-IDA-EPI) method in negative ion mode on a hybrid triple quadrupole-linear ion trap mass spectrometer (QTRAP). A total of 12 metabolites were characterized based on their MS/MS spectra, and the retention times were compared with those of the parent compound. The metabolites were divided into five structural classes based on biotransformation reactions: amide hydrolysis, ester hydrolysis, mono-oxidation, glucuronidation, and a combination of these reactions. From this study, 2-(4-((3r,5r,7r)-adamantan-1-yl)phenoxy)acetic acid (APA, M7), the metabolite produced via amide hydrolysis, was found to be a major circulating metabolite of LW6 in mice. The results of this study can be used to improve the pharmacokinetic profile by lowering the clearance and increasing the exposure relative to LW6.

UHPLC-MS Simultaneous Determination and Pharmacokinetic Study of Three Aromatic Acids and One Monoterpene in Rat Plasma after Oral Administration of Shaofu Zhuyu Decoction

2013 ◽  
Vol 41 (03) ◽  
pp. 697-715 ◽  
Author(s):  
Shulan Su ◽  
Wenxia Cui ◽  
Jin-Ao Duan ◽  
Yongqing Hua ◽  
Jianming Guo ◽  
...  
Keyword(s):  
Oral Administration ◽  
Pharmacokinetic Study ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Rat Plasma ◽  
Negative Ion ◽  
Aromatic Acids ◽  
Active Components ◽  
Negative Ion Mode

We developed a sensitive and rapid method for determination of ferulic acid, caffeic acid, vanillic acid, and paeoniflorin in rat plasma based on ultra high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC–MS/MS). The separation of the four compounds was carried out on an AcQuity UHPLC™ BEH C18 column using a mobile phase consisting of acetonitrile and water (containing 0.1% formic acid). Electrospray ionization in positive and negative ion mode and multiple reaction monitoring was used to identify and quantify active components. All calibration curves gave good linearity (r > 0.991) over the concentration range from 4.24–2875 ngmL-1 for all components. The precision of the in vivo study was evaluated by intraday and interday assays and the percentages of RSD were all within 10.6%. The recovery ranged from 60.2 to 77.9%. The method was successfully applied to pharmacokinetic study of all three aromatic acids and one monoterpene in rat plasma. Furthermore, we compared the pharmacokinetics profile of the four compounds in normal and primary dysmenorrhea rats' plasma following oral administration of Shaofu Zhuyu decoction (SFZYD) and its ethanol supernatant extract (SFE).

scholarly journals Effect of high levels of organic selenium on glutation-peroxidase (GSH-Px) activity in blood plasma of broilers

2005 ◽  
Vol 59 (3-4) ◽  
pp. 383-390 ◽  
Author(s):  
Mirjana Joksimovic-Todorovic ◽  
Zivan Jokic ◽  
Zlatan Sinovec
Keyword(s):  
Blood Plasma ◽  
Sodium Selenite ◽  
Control Group ◽  
Organic Selenium ◽  
Fattening Period ◽  
The Individual ◽  
Selenized Yeast ◽  
Broiler Feed ◽  
Plasma Activity ◽  
In Blood Plasma

An experiment lasting 45 days was performed on 125 Hybro broilers divided into five groups. All compounds for broiler feed mixes used in the experiment contained 0.15 mg Se/kg, in the form of sodium selenite. The control group (K-group) of broilers was fed mixes without added organic selenium, and the experimental groups with mixes to which selenium, in the form of selenized-yeast, was added in quantities of 2, 5, 10, or 15 mg/kg. Selenized yeast (ICN - Gaienika) was obtained from beer yeast and contained 1.51, or 1.45 mg/g total, or organically bound selenium. At the beginning of the fattening period, GSH-Px plasma activity in broilers of the K-group ranged around 16.55 ?kat/L, while GSH-Px plasma activity in broilers of experimental groups was statistically significantly higher, but without any major differences among the individual groups (on the average 25.53fjkat/L). In the blood plasma of K-group, GSH-Px activity dropped already in the second week of life and was maintained at a relatively constant level (about 10 ?kat/L) until the end of the experiment. The same phenomenon was observed in the experimental groups, but the trend of declining GSH-Px activity in blood plasma was more expressed, and, contrary to the control group, was expressed also in the later phases of the experiment. In the 3rd week of the fattening period, GSH-Px plasma activity in broilers of the control and experimental groups was relatively equal, and then the plasma activity of GSH-Px in broilers of the experimental groups decreased, but there were no major differences among the individual groups.

scholarly journals A Mass Spectrometry-Based Approach for Characterization of Red, Blue, and Purple Natural Dyes

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3223
Author(s):  
Katarzyna Lech ◽  
Emilia Fornal
Keyword(s):  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Natural Dyes ◽  
Negative Ion ◽  
Near Eastern ◽  
Esi Ms ◽  
Historical Objects ◽  
Tandem Mass Spectrometric ◽  
Negative Ion Mode ◽  
Analytical Approaches

Effective analytical approaches for the identification of natural dyes in historical textiles are mainly based on high-performance liquid chromatography coupled with spectrophotometric detection and tandem mass spectrometric detection with electrospray ionization (HPLC-UV-Vis-ESI MS/MS). Due to the wide variety of dyes, the developed method should include an adequate number of reference color compounds, but not all of them are commercially available. Thus, the present study was focused on extending of the universal analytical HPLC-UV-Vis-ESI MS/MS approach to commercially unavailable markers of red, purple, and blue dyes. In the present study, HPLC-UV-Vis-ESI MS/MS was used to characterize the colorants in ten natural dyes (American cochineal, brazilwood, indigo, kermes, lac dye, logwood, madder, orchil, Polish cochineal, and sandalwood) and, hence, to extend the analytical method for the identification of natural dyes used in historical objects to new compounds. Dye markers were identified mostly on the basis of triple quadrupole MS/MS spectra. In consequence, the HPLC-UV-Vis-ESI MS/MS method with dynamic multiple reaction monitoring (dMRM) was extended to the next 49 commercially unavailable colorants (anthraquinones and flavonoids) in negative ion mode and to 11 (indigoids and orceins) in positive ion mode. These include protosappanin B, protosappanin E, erythrolaccin, deoxyerythrolaccin, nordamnacanthal, lucidin, santalin A, santalin B, santarubin A, and many others. Moreover, high-resolution QToF MS data led to the establishment of the complex fragmentation pathways of α-, β-, and γ- aminoorceins, hydroxyorceins, and aminoorceinimines extracted from wool dyed with Roccella tinctoria DC. The developed approach has been tested in the identification of natural dyes used in 223 red, purple, and blue fibers from 15th- to 17th-century silk textiles. These European and Near Eastern textiles have been used in vestments from the collections of twenty Krakow churches.

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