Pharmacokinetics and Bioavailability Study of Tubeimoside I in ICR Mice by UPLC-MS/MS

The aim of this study is to establish and validate a rapid, selective, and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to determine tubeimoside I (TBMS-I) in ICR (Institute of Cancer Research) mouse whole blood and its application in the pharmacokinetics and bioavailability study. The blood samples were precipitated by acetonitrile to extract the analytes. Chromatographic separation was performed on a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm). The mobile phase consisted of water with 0.1% formic acid and methanol (1 : 1, v/v) at a flow rate of 0.4 mL/min. The total eluting time was 4 min. The TBMS-I and ardisiacrispin A (internal standard (IS)) were quantitatively detected by a tandem mass spectrometry equipped with an electrospray ionization (ESI) in a positive mode by multiple reaction monitoring (MRM). A validation of this method was in accordance with the US Food and Drug Administration (FDA) guidelines. The lower limit of quantification (LLOQ) of TBMS-I was 2 ng/mL, and the calibration curve was linearly ranged from 2 to 2000 ng/mL (r2 ≥ 0.995). The relative standard deviation (RSD) of interday precision and intraday precision was both lower than 15%, and the accuracy was between 91.7% and 108.0%. The average recovery was >66.9%, and the matrix effects were from 104.8% to 111.0%. In this assay, a fast, highly sensitive, and reproducible quantitative method was developed and validated in mouse blood for the first time. The absolute availability of TBMS-I in the mouse was only 1%, exhibiting a poor oral absorption.

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Pharmacokinetic Effects of l-Tetrahydropalmatine on Ketamine in Rat Plasma by Ultraperformance Liquid Chromatography Tandem Mass Spectrometry

BioMed Research International ◽

10.1155/2020/9259683 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Yan Du ◽

Hongliang Su ◽

Jie Cao ◽

Zhiwen Wei ◽

Yujin Wang ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Rat Plasma ◽

Tandem Mass ◽

Chromatography Tandem Mass Spectrometry ◽

Relative Standard ◽

Liquid Chromatography Tandem Mass

Male Sprague-Dawley rats (n=18) were randomly divided into three groups: a saline group (20 mL/kg by gavage), a ketamine (KET) group (100 mg/kg by gavage), and a KET (the same routes and doses) combined with levo-tetrahydropalmatine (l-THP; 40 mg/kg by gavage) group (n=6). Blood samples were acquired at different time points after drug administration. A simple and sensitive ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to determine the concentrations of KET and its metabolite, norketamine (NK), in rat plasma. Chromatographic separation was achieved using a BEH C18 column (2.1 mm×50 mm, 1.7 μm) with chlorpheniramine maleate (Chlor-Trimeton) as an internal standard (IS). The initial mobile phase consisted of acetonitrile–water with 0.1% methanoic acid (80 : 20, v/v). The multiple reaction monitoring (MRM) modes of m/z 238.1→m/z 179.1 for KET, m/z 224.1→m/z 207.1 for NK, and m/z 275→m/z 230 for Chlor-Trimeton (IS) were utilized to conduct a quantitative analysis. Calibration curves of KET and NK in rat plasma demonstrated good linearity in the range of 2.5–500 ng/mL (r>0.9994), and the lower limit of quantification (LLOQ) was 2.5 ng/mL for both. Moreover, the intra- and interday precision relative standard deviation (RSD) of KET and NK were less than 4.31% and 6.53%, respectively. The accuracies (relative error) of KET and NK were below -1.41% and -6.07%, respectively. The extraction recoveries of KET and NK were more than 81.23±3.45% and 80.42±4.57%, respectively. This sensitive, rapid, and selective UPLC-MS/MS method was successfully applied to study the pharmacokinetic effects of l-THP on KET after gastric gavage. The results demonstrated that l-THP could increase the bioavailability of KET and promote the metabolism of KET. The results showed that l-THP has pharmacokinetics effects on KET in rat plasma.

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Pharmacokinetics of isocorynoxeine in rat plasma after intraperitoneal administration by UPLC–MS/MS

Acta Chromatographica ◽

10.1556/1326.2019.00716 ◽

2020 ◽

Vol 32 (4) ◽

pp. 260-263

Author(s):

Haichao Zhan ◽

Zhen Wei ◽

Ke Ren ◽

Shuhua Tong ◽

Xianqin Wang ◽

...

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Multiple Reaction Monitoring ◽

Intraperitoneal Administration ◽

Gradient Elution ◽

Ultra Performance Liquid Chromatography ◽

Rat Plasma ◽

Tandem Mass ◽

Relative Standard ◽

Liquid Chromatography Tandem Mass

Isocorynoxeine is one of the main alkaloids in Chinese medicinal herbs, and has pharmacological activities such as antihypertensive, sedative, anticonvulsant, and neuronal protection. It is an effective component of Uncaria for the treatment of hypertension. In this study, we used a fast and sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) to detect isocorynoxeine in rat plasma and investigated its pharmacokinetics in rats. Six rats were given isocorynoxeine (15 mg/kg) by intraperitoneal (i.p.) administration. Blood (100 μL) was withdrawn from the caudal vein at 5 and 30 min and 1, 2, 4, 6, 8, 12, and 24 h after administration. Chromatographic separation was achieved using a UPLC BEH C18 column using a mobile phase of acetonitrile–0.1% formic acid with gradient elution. Electrospray ionization (ESI) tandem mass spectrometry in the multiple reaction monitoring (MRM) mode with positive ionization was applied. Intra-day and inter-day precisions (relative standard deviation, %RSD) of isocorynoxeine in rat plasma were lower than 12%. The method was successfully applied in the pharmacokinetics of isocorynoxeine in rats after intraperitoneal administration. The t1/2 of isocorynoxeine is 4.9 ± 2.1 h, which indicates quick elimination.

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METHOD DEVELOPMENT AND VALIDATION OF LERCANIDIPINE IN HUMAN PLASMA BY LIQUID CHROMATOGRAPHY TANDEM-MASS SPECTROMETRY

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i4.26544 ◽

2018 ◽

Vol 10 (4) ◽

pp. 87

Author(s):

Yahdiana Harahap ◽

Norma Andriyani ◽

Harmita .

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Method Development ◽

Matrix Effects ◽

Multiple Reaction Monitoring ◽

Tandem Mass ◽

Mass Detection ◽

Column Temperature ◽

Z Value

Objective: To obtain an optimum and validated method for analyzing lercanidipine in plasma using Ultra Performance Liquid Chromatography of Tandem Mass Spectrometry (UPLC-MS/MS).Methods: The separation was carried out using 1.7μm (2.1 x 100 mm) Waters AcquityTM UPLC C18 column, a mobile phase of the 0.1% formic acid-methanol mixture (20:80 v/v) with isocratic elution, 30 °C column temperature, 0.2 ml/min flow rate and amlodipine as an internal standard. Mass detection was performed with a positive XBL TQD type Electrospray Ionization (ESI) in Multiple Reaction Monitoring modes. Lercanidipine was detected at m/z value of 612.11>280.27 and amlodipine was detected at m/z value 409.1>238.15. The optimum sample preparation method was a liquid-liquid extraction using 5 ml of n-hexane-ethyl acetate (50:50 v/v), vortex mixed for 3 min, centrifuged at 4000 rpm for 20 min, evaporated with nitrogen at 50 °C for 30 min, and the residue was reconstituted with 100 μl of mobile phase.Results: The method was linear in the range of 0.025-10 ng/ml with r ≥ 0.9986. Accuracy and precision within-run and between-run met the requirements with %diff and %CV, not exceeding ± 15% and not more than ± 20% for Lower Limit of Quantification (LLOQ) concentration.Conclusion: It was concluded that the developed method met the requirements of selectivity, carry over, stability, the integrity of dilution, and matrix effects under the Guideline on Bioanalytical Method Validation by the European Medicines Agency in 2011.

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A Hydrophilic Interaction Liquid Chromatography–Tandem Mass Spectrometry Quantitative Method for Determination of Baricitinib in Plasma, and Its Application in a Pharmacokinetic Study in Rats

Molecules ◽

10.3390/molecules25071600 ◽

2020 ◽

Vol 25 (7) ◽

pp. 1600 ◽

Cited By ~ 1

Author(s):

Essam Ezzeldin ◽

Muzaffar Iqbal ◽

Yousif A. Asiri ◽

Azza A Ali ◽

Prawez Alam ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Janus Kinase ◽

Pharmacokinetic Studies ◽

Tandem Mass ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass

Baricitinib, is a selective and reversible Janus kinase inhibitor, is commonly used to treat adult patients with moderately to severely active rheumatoid arthritis (RA). A fast, reproducible and sensitive method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantification of baricitinib in rat plasma has been developed. Irbersartan was used as the internal standard (IS). Baracitinib and IS were extracted from plasma by liquid–liquid extraction using a mixture of n-hexane and dichloromethane (1:1) as extracting agent. Chromatographic separation was performed using Acquity UPLC HILIC BEH 1.7 µm 2.1 × 50 mm column with the mobile phase consisting of 0.1% formic acid in acetonitrile and 20 mM ammonium acetate (pH 3) (97:3). The electrospray ionization in the positive-mode was used for sample ionization in the multiple reaction monitoring mode. Baricitinib and the IS were quantified using precursor-to-production transitions of m/z 372.15 > 251.24 and 429.69 > 207.35 for baricitinib and IS, respectively. The method was validated according to the recent FDA and EMA guidelines for bioanalytical method validation. The lower limit of quantification was 0.2 ng/mL, whereas the intra-day and inter-day accuracies of quality control (QCs) samples were ranged between 85.31% to 89.97% and 87.50% to 88.33%, respectively. Linearity, recovery, precision, and stability parameters were found to be within the acceptable range. The method was applied successfully applied in pilot pharmacokinetic studies.

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Dissipation Kinetics and the Pre-Harvest Residue Limits of Acetamiprid and Chlorantraniliprole in Kimchi Cabbage Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

Molecules ◽

10.3390/molecules24142616 ◽

2019 ◽

Vol 24 (14) ◽

pp. 2616

Author(s):

Jonghwa Lee ◽

Byung Joon Kim ◽

Eunhye Kim ◽

Jeong-Han Kim

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

High Performance ◽

Multiple Reaction Monitoring ◽

Ultra Performance Liquid Chromatography ◽

Tandem Mass ◽

Dissipation Kinetics ◽

Relative Standard ◽

Harvest Residue

The dissipation behaviors of acetamiprid and chlorantraniliprole in kimchi cabbages were studied under open-field conditions. A simple and rapid analytical method was developed using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The multiple reaction monitoring (MRM) conditions of two pesticides were optimized to quantify and identify the pesticide residues. Sample preparation was performed by the QuEChERS (quick, easy, cheap, effective, rugged, and safe) method. Average recovery rates at the different spiked levels (0.05 and 0.25 mg/kg) were in the range of 103.6–113.9% (acetamiprid) and 80.8–91.2% (chlorantraniliprole), and the relative standard deviations were ≤4.3% for all. The dissipation kinetics were assessed using first-order equations after spraying acetamiprid and chlorantraniliprole individually on kimchi cabbages. The biological half-lives in field 1 and 2 were 5.2 and 6.3 days (acetamiprid) and 10.0 and 15.2 days (chlorantraniliprole), respectively. Based on the dissipation equations, the pre-harvest residue limits (PHRLs) corresponding to each day before harvest were suggested as the guidelines to meet the MRL on harvest day. It was also predicted that the terminal residues observed after multiple sprayings (three and seven days) would be below the MRL when harvested, in compliance with the established pre-harvest intervals.

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Method for the Determination of Total Homocysteine in Plasma and Urine by Stable Isotope Dilution and Electrospray Tandem Mass Spectrometry

Clinical Chemistry ◽

10.1093/clinchem/45.9.1517 ◽

1999 ◽

Vol 45 (9) ◽

pp. 1517-1522 ◽

Cited By ~ 111

Author(s):

Mark J Magera ◽

Jean M Lacey ◽

Bruno Casetta ◽

Piero Rinaldo

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Signal To Noise Ratio ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

High Volume ◽

Hplc Method ◽

Tandem Mass ◽

Electrospray Tandem Mass Spectrometry ◽

Total Homocysteine

Abstract Background: Total homocysteine (tHcy) has emerged as an important independent risk factor for cardiovascular disease. Analytical methods are needed to accommodate the high testing volumes for tHcy and provide rapid turnaround. Methods: We developed liquid chromatography electrospray tandem mass spectrometry (LC-MS/MS) method based on the analysis of 100 μL of either plasma or urine with homocystine-d8 (2 nmol) added as internal standard. After sample reduction and deproteinization, the analysis was performed in the multiple reaction monitoring mode in which tHcy and Hcy-d4 were detected through the transition from the precursor to the product ion (m/z 136 to m/z 90 and m/z 140 to m/z 94, respectively). The retention time of tHcy and Hcy-d4 was 1.5 min in a 2.5-min analysis. Results: Daily calibrations between 2.5 and 60 μmol/L exhibited consistent linearity and reproducibility. At a plasma concentration of 0.8 μmol/L, the signal-to-noise ratio for tHcy was 17:1. The regression equation for the comparison between our previous HPLC method (y) and the LC-MS/MS method (x) was y = 1.097x − 1.377 (r = 0.975; Sy|x =1.595 μmol/L; n = 367), and for comparison between a fluorescence polarization immunoassay (Abbott IMx; y) and LC-MS/MS (x) was y = 1.039x + 0.025 (r = 0.969; Sy|x =1.146 μmol/L; n = 367). Inter- and intraassay CVs were 2.9–5.9% and 3.6–5.3%, respectively, at mean concentrations of 3.9, 22.7, and 52.8 μmol/L. Mean recovery of tHcy was 94.2% (20 μmol/L) and 97.8% (50 μmol/L). Conclusions: The sensitivity and specificity of tandem mass spectrometry are well suited to perform high-volume analysis of tHcy. Reagents are inexpensive and sample preparation of a batch of 40 specimens is completed in less than 1 h and is amenable to automation.

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Simultaneous Determination of Isopyrazam and Azoxystrobin in Cucumbers by Liquid Chromatography–Tandem Mass Spectrometry

Journal of Food Protection ◽

10.4315/0362-028x.jfp-17-228 ◽

2017 ◽

Vol 80 (12) ◽

pp. 2112-2118 ◽

Cited By ~ 4

Author(s):

Dan Hu ◽

Xu Xu ◽

Tian Cai ◽

Wei-Ying Wang ◽

Chun-Jie Wu ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Matrix Effects ◽

Fast Method ◽

Tandem Mass ◽

Chromatography Tandem Mass Spectrometry ◽

Relative Standard ◽

Liquid Chromatography Tandem Mass

ABSTRACTA rapid and sensitive analytical method based on high-performance liquid chromatography–tandem mass spectrometry was developed and validated for the determination of isopyrazam (IZM) and azoxystrobin (AZT) in cucumbers. A modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) method was used as the pretreatment procedure. The samples were extracted with acetonitrile and cleaned up with octadecylsilyl silica (C18) and graphite carbon black. The proposed method resulted in satisfactory recovery of IZM and AZT (91.48 to 114.62%), and relative standard deviations were less than 13.1% at fortification concentrations of 1, 20, and 500 μg kg−1 (n = 3). The limits of quantification for IZM and AZT were 0.498 and 0.499 μg kg−1, respectively, which are far below the maximum residue level (0.5 mg kg−1) established for this type of sample. Matrix effects were also evaluated. This study established a sensitive and fast method for the detection of IZM and AZT in cucumber samples.

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Quantitative analysis of vitamin D and its main metabolites in human milk by supercritical fluid chromatography coupled to tandem mass spectrometry

Analytical and Bioanalytical Chemistry ◽

10.1007/s00216-019-02248-5 ◽

2019 ◽

Vol 412 (2) ◽

pp. 365-375 ◽

Cited By ~ 3

Author(s):

J. M. Oberson ◽

S. Bénet ◽

K. Redeuil ◽

E. Campos-Giménez

Keyword(s):

Mass Spectrometry ◽

Vitamin D ◽

Tandem Mass Spectrometry ◽

Human Milk ◽

Supercritical Fluid ◽

Supercritical Fluid Chromatography ◽

Multiple Reaction Monitoring ◽

Ammonium Formate ◽

Tandem Mass ◽

Relative Standard

AbstractA novel method to quantitate vitamin D and its main metabolites (vitamin D3, vitamin D2, and their 25-hydroxy metabolites) in breast milk by supercritical fluid chromatography has been developed and fully validated. A small volume of sample (1 mL) is subjected to ethanolic protein precipitation and liquid-liquid extraction. Final extracts are derivatized with 4-phenyl-1,2,4-triazoline-3,5-dione and vitamin D derivatives analyzed by supercritical fluid chromatography hyphenated to tandem mass spectrometry with atmospheric pressure chemical ionization. Multiple reaction monitoring is used for quantitation. Separation conditions were optimized using a gradient of methanol-water-ammonium formate into carbon dioxide. Make-up solvent was methanol containing ammonium formate. The quantitation limit reached levels as low as 50 pmol/L, with intra- and inter-day relative standard deviations lower than 15% and 20% for all analytes. Accuracy was evaluated by spiking experiments and was well within acceptability ratios (± 15%). The method was then applied to a subset of commercially available human milk samples. The newly developed method provides opportunities to determine the nutritional status of mother-infant dyads from a non-invasive measure, or for interventional or observational studies building knowledge on the composition of human milk.

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A Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Nimbolide in Mouse Serum: Application to a Preclinical Pharmacokinetics Study

Pharmaceutics ◽

10.3390/pharmaceutics10030123 ◽

2018 ◽

Vol 10 (3) ◽

pp. 123 ◽

Cited By ~ 4

Author(s):

Lingzhi Wang ◽

Do-Dang Phan ◽

Nicholas Syn ◽

Xiaoqiang Xiang ◽

Hongyan Song ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Mouse Serum ◽

Tandem Mass ◽

Liquid Chromatography Tandem Mass ◽

Tandem Mass Spectrometric

A sensitive and robust liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of nimbolide in mouse serum. Exemestane was used as the internal standard (IS). Here, we employed acetonitrile-based protein precipitation (PPT) for serum sample preparation, and performed chromatographic separation using an ODS Hypersil C18 column (100 mm × 2.1 mm, 5 µm) with gradient elution (0.1% formic acid in water vs 100% acetonitrile). The run time was 6 min. Instrumental analysis was performed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the multiple-reaction monitoring (MRM) under positive mode. A good linear calibration was achieved in the 5–1000 ng/mL range. The intra- and inter-day precisions for nimbolide were ≤12.6% and ≤13.9% respectively. Intra-day accuracy ranged from 96.9–109.3%, while inter-day accuracy ranged from 94.3–110.2%. The matrix effect of nimbolide, detected but consistent at low and high concentrations, do not affect linearity of standard curve. In conclusion, we have developed and validated a sensitive analytical method for determination of a novel natural compound nimbolide in mouse serum, and it has been successfully applied to our preclinical study in investigating the pharmacokinetic properties of nimbolide, which could greatly facilitate the preclinical development of the promising lead compound for anticancer therapy.

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HPLC–Tandem Mass Spectrometric Method to Characterize Resveratrol Metabolism in Humans

Clinical Chemistry ◽

10.1373/clinchem.2006.071936 ◽

2007 ◽

Vol 53 (2) ◽

pp. 292-299 ◽

Cited By ~ 68

Author(s):

Mireia Urpi-Sarda ◽

Raul Zamora-Ros ◽

Rosa Lamuela-Raventos ◽

Antonio Cherubini ◽

Olga Jauregui ◽

...

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Solid Phase ◽

Biological Effects ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Assessment Tools ◽

Tandem Mass ◽

Mass Spectrometric Method ◽

Tandem Mass Spectrometric

Abstract Background: Nutritional biomarkers are alternatives to traditional dietary assessment tools. We sought to develop a method for nutritional analysis of resveratrol, a phenolic compound with purported health-promoting properties, and to determine all resveratrol metabolites. Methods: We obtained LDL and urine samples from 11 healthy male volunteers who had consumed 250 mL of Merlot red wine. We measured resveratrol and its metabolites with 96-well solid-phase extraction plates coupled with HPLC-tandem mass spectrometry. Hexestrol was used as the internal standard. Gradient chromatography in multiple reaction monitoring mode was performed on a Luna C18 column, maintained at 40 °C; m/z transitions were as follows: resveratrol, 227/185; resveratrol glucosides, 389/227; resveratrol glucuronides, 403/227; resveratrol sulfates, 307/227; taxifolin, 303/285; and hexestrol, 269/134. Results: Standard calibration curves were linear at 4.4–3289.5 nmol/L. Residual analyses were 100% (3.2) for trans-resveratrol and 100% (11.1) for trans-piceid. In both matrices, imprecision (CV) was <10.8% at all concentrations. Detection limits for resveratrol were 0.2 nmol/L (LDL), 0.3 nmol/L (synthetic urine), and 4.0 nmol/L (blank urine). Resveratrol and metabolites were checked for stability, and no degradation was observed. Conclusions: The HPLC–tandem mass spectrometry method enabled us to identify resveratrol sulfates in human LDL and to characterize the complete profile of resveratrol metabolism in human LDL and urine. This method provides an accurate index of exposure to resveratrol and its metabolites, which can be used as nutritional biomarkers for evaluating the biological effects of moderate wine intake on human health.

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