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 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.

scholarly journals Secondary metabolite profiling and characterization of diterpenes and flavones from the methanolic extract of Andrographis paniculata using HPLC-LC-MS/MS

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Manish Kumar Dwivedi ◽  
Shruti Sonter ◽  
Shringika Mishra ◽  
Priyanka Singh ◽  
Prashant Kumar Singh
Keyword(s):  
Methanolic Extract ◽  
Rapid Identification ◽  
Andrographis Paniculata ◽  
Negative Ion ◽  
Spectroscopic Techniques ◽  
Lead Compounds ◽  
Methoxy Flavone ◽  
Negative Ion Mode

Abstract Background Andrographis paniculata is a well-known medicinal plant that contains various classes of bioactive secondary metabolites. It is widely used by the traditional medicinal healers for treatment of malaria and other diseases. There is an urgent need for screening of potent novel compounds from the methanol extract of A. paniculata. Earlier, we obtained appreciable in vitro anti-malarial activity (IC50-10.75 μg/ml) in the same plant. In current study, we developed novel analytical methods for rapid identification and characterization of diterpenes and flavones using chromatographic and spectroscopic techniques and identified major compounds that might possess anti-malarial activities. Results Based on the chromatographic and mass spectrometric features, we have identified a total of 74 compounds (25 compounds from positive ion mode; 49 compounds from negative ion mode). The mass spectrum data predicted andrographolide (15%) presence in the highest amount in both positive and negative ion modes. Based on the percentage purity, Andrographolide and skullcapflavone I was selected as representative class of diterpenes and flavones for fragmentation studies. Conclusions The result led to identification of Neoandrographolide, andrographolactone, 14-dehydroxy-11,12-didehydroandrographolide, skullcapflavone I, and 5-Hydroxy-2′,7,8-tri methoxy flavone from the methanolic extract of A. paniculata that is used in traditional medicine by tribal healers of Amarkantak region for treating malaria. These could be lead compounds for the development of novel anti-malarial drugs.

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 Development and Validation of UPLC-MS / MS Method for Obtaining Favipiravir Tablet Dosage form and Evaluation of its Behavior Under forced Conditions

2021 ◽  
pp. 130-140
Author(s):  
Süleyman Gökce ◽  
Ayşen Höl ◽  
Ibrahim Bulduk
Keyword(s):  
Active Substance ◽  
Uv Light ◽  
Thermal Conditions ◽  
Test Method ◽  
Negative Ion ◽  
Ionization Source ◽  
Degradation Rates ◽  
Negative Ion Mode

Aims: Favipiravir (FVP) is a drug developed against RNA viruses. It is a drug that is used actively in the treatment of coronavirus. In vitro and in vivo investigations have shown that it inhibits the virus. In this study, a recovery study of tablet formulations was carried out by developing a UPLC-MS/MS method, which is used extensively in pandemic conditions. In addition, stability studies of favipiravir agent under forced conditions were conducted. The validated method is selective, robust, simple and applicable for tablet analysis. C18 (4.6 mm × 50 mm, 2.7 μm) column was used as the stationary phase and water-methanol (80-20 v/v) containing 0.1% formic acid was used as the mobile phase. UPLC optimization; It was conducted at a wavelength of 222 nm and a flow rate of 0.8 mL/min at 40 °C, retention time was 1.155 min. The electrospray jet stream ionization source was analyzed using mass spectrometry in negative ion mode. The molecular peak for Favipiravir was [M-1] 155.9, and the daughter ion determined 112.6. The stability test method was carried out in accordance with the ICH procedure. Reaction and degradation rates of the active substance under various forced conditions (acidic, basic, oxidative, UV light and thermal conditions) were investigated. The products formed by the decomposition of the active substance under stress conditions were determined by mass spectroscopy.

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.

scholarly journals Simultaneous Quantification and Pharmacokinetic Study of Nine Bioactive Components of Orthosiphon stamineus Benth. Extract in Rat Plasma by UHPLC-MS/MS

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3057 ◽  
Author(s):  
Guo ◽  
Li ◽  
Gu ◽  
Zhu ◽  
Su ◽  
...  
Keyword(s):  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Rat Plasma ◽  
Negative Ion ◽  
Pharmacokinetic Analysis ◽  
Bioactive Components ◽  
Triple Quadrupole Mass Spectrometer ◽  
Salvianolic Acid ◽  
Orthosiphon Stamineus ◽  
Simultaneous Quantification

Orthosiphon stamineus Benth. (OS) is a traditional folk medicine for the treatment of kidney stones and other urinary tract diseases. In this study, a rapid and sensitive Ultra high-performance liquid chromatography (UHPLC)-MS/MS approach was established and validated for the simultaneous quantification of nine bioactive components in rat plasma. The nine components from OS extract detected in rat plasma were danshensu, protocatechuic acid, caffeic acid, rosmarinic acid, salvianolic acid A, salvianolic acid B, cichoric acid, sinensetin and eupatorin. After liquid-liquid extraction with ethyl acetate, the plasma samples were subjected to a triple quadrupole mass spectrometer employing electrospray ionization (ESI) technique and operating in multiple reaction monitoring (MRM) with both positive and negative ion modes. The standard curves showed good linear regression (r > 0.9915) over the concentration range for the nine analytes. The inter-day and intra-day precision and accuracy were found to be within 15% of the nominal concentration. The recovery and stability of nine compounds were all demonstrated to be within acceptable limits. The approach was successfully applied to investigate the pharmacokinetic analysis of the nine bioactive components after oral administration of OS extract in rats.

scholarly journals Diterpenoids as potential anti-malarial compounds from Andrographis paniculata

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Manish Kumar Dwivedi ◽  
Shringika Mishra ◽  
Shruti Sonter ◽  
Prashant Kumar Singh
Keyword(s):  
Chloroform Extract ◽  
Andrographis Paniculata ◽  
Negative Ion ◽  
Malarial Parasite ◽  
Development Programs ◽  
Traditional Use ◽  
Negative Ion Mode ◽  
Positive Ion

Abstract Background The objectives of the current study are to evaluate the traditionally used medicinal plants Andrographis paniculata for in vitro anti-malarial activity against human malarial parasite Plasmodium falciparum and to further characterize the anti-malarial active extract of A. paniculata using spectroscopic and chromatographic methods. Results The chloroform extract of A. paniculata displayed anti-malarial activity with IC50 values 6.36 μg/ml against 3D7 strain and 5.24 μg/ml against K1 strains respectively with no evidence of significant cytotoxicity against mammalian cell line (CC50 > 100 μg/ml). LC-MS analysis of the extract led to the identification of 59 compounds based on their chromatographic and mass spectrometric features (a total of 35 compounds are present in positive ion and 24 compounds in negative ion mode). We have identified 5 flavonoids and 30 compounds as diterpenoids in positive ion mode, while in the negative mode all identified compounds were diterpenoids. Characterization of the most promising class of compound diterpenoids using HPLC-LC-ESI-MS/MS was also undertaken. Conclusions The in vitro results undoubtedly validate the traditional use of A. paniculata for the treatment of malaria. The results have led to the identification of diterpenoids from IGNTU_06 extract as potential anti-malarial compounds that need to be further purified and analyzed in anti-malarial drug development programs. Graphical abstract

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 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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