Determination of myrislignan levels in BALB/c mouse plasma by LC-MS/MS and a comparison of its pharmacokinetics after oral and intraperitoneal administration

Abstract Background Myrislignan is a natural product from Myristica sp. with diverse pharmacological activities. Recently, the anti-Toxoplasma gondii (T. gondii) activity of myrislignan has been proposed, and in vivo studies of its pharmacokinetics in BALB/c mice are necessary to further evaluate the clinical effects of myrislignan. Results In this study, a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify myrislignan levels in mouse plasma using dehydrodiisoeugenol as an internal standard (IS) in positive ion mode. Chromatographic separation of the analytes was achieved using an ACE Ultracore Super C18 analytical column (2.5 μm, 2.1 × 50 mm) at 30 °C. A gradient mobile phase consisting of water (0.1 % formic acid) and acetonitrile (0.1 % formic acid) was delivered at a flow rate of 0.4 mL/min. Myrislignan and the IS eluted at 1.42 and 1.71 min, respectively. A good excellent linear response across the concentration range of 1-1000 ng/mL was achieved (r2 = 0.9973). The lower limit of quantification (LLOQ) was 1 ng/mL, and the inter- and intra-day accuracy and precision of the method showed relative standard deviations (RSDs) less than 10 %. The method was applied to examine the pharmacokinetics of myrislignan in mouse plasma following a single oral administration of 200 mg/kg or intraperitoneal administration of 50 mg/kg myrislignan, and the bioavailability (F) of orally administered myrislignan was only 1.97 % of the bioavailability of intraperitoneally administered myrislignan. Conclusions A rapid and sensitive LC-MS/MS method has been was developed, validated and successfully used to determine myrislignan levels in mice after oral or intraperitoneal administration. This study is the first to report the pharmacokinetic parameters of myrislignan in mice and to compare its pharmacokinetics after oral and intraperitoneal administration, which will be useful for further research on the administration of myrislignan in animals and humans.

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Determination of Lekethromycin, a Novel Macrolide Lactone, in Rat Plasma by UPLC-MS/MS and Its Application to a Pharmacokinetic Study

Molecules ◽

10.3390/molecules25204676 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4676

Author(s):

Hongzhi Xiao ◽

Pan Sun ◽

Jicheng Qiu ◽

Jianzhong Wang ◽

Lei Yan ◽

...

Keyword(s):

Electrospray Ionization ◽

Matrix Effects ◽

High Resolution Mass Spectrometry ◽

Internal Standard ◽

Gradient Elution ◽

Storage Conditions ◽

Rat Plasma ◽

Pharmacokinetic Parameters ◽

Limit Of Quantification ◽

Relative Standard

Lekethromycin, a new macrolide lactone, exhibits significant antibacterial activity. In this study, a reliable analytical ultrahigh-performance liquid chromatography electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UPLC-ESI-Orbitrap-MS) method was established and validated for the detection of lekethromycin in rat plasma. After a simple acetonitrile (ACN)-mediated plasma protein precipitation, chromatographic separation was performed on a Phenomenex Luna Omega PS C18 column (30 × 2.1 mm i.d. particle size = 3 μm) conducted in a gradient elution procedure using 0.5% formic acid (FA) in ACN and 0.5% FA in water as the mobile phase pumped at a flow rate of 0.3 mL/min. Detection was carried out under positive electrospray ionization (ESI+) conditions in parallel reaction monitoring (PRM) mode with observation of m/z 804.5580 > 577.4056 for lekethromycin and 777.5471 > 619.4522 for gamithromycin (internal standard, IS). The linear range was 5–1000 ng/mL (r2 > 0.99), and the lower limit of quantification (LLOQ) was 5 ng/mL. The intra- and inter-day precision (expressed as relative standard deviation, RSD) values were ≤7.3% and ≤6.3%, respectively, and the accuracy was ≥90% ± 5.3%. The mean extraction recovery RSD valWeue was <5.1%. Matrix effects and dilution integrity RSD values were <5.6% and <3.2%, respectively. Lekethromycin was deemed stable under certain storage conditions. This fully validated method was effectively applied to study the pharmacokinetics of lekethromycin after a single intravenous administration of 5 mg/kg in rats. The main pharmacokinetic parameters were T1/2λz, CL_obs and VZ_obs were 32.33 ± 14.63 h, 0.58 ± 0.17 L/h/kg and 25.56 ± 7.93 L/kg, respectively.

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A Rapid and Sensitive UHPLC-MS/MS Method for Determination of 2, 3, 8-Trimethylellagic, a Potent Active Compound from Sanguisorba officinalis L., and Its Application in the Pharmacokinetic Study within Thrombocytopenia Rats

Journal of Chemistry ◽

10.1155/2021/3309434 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Yuqing Wang ◽

Jianming Wu ◽

Yunxia Li ◽

Jing Yang ◽

Long Wang ◽

...

Keyword(s):

Plasma Concentration ◽

Maximum Concentration ◽

High Performance ◽

Internal Standard ◽

Pharmacokinetic Parameters ◽

Time Curve ◽

Concentration Time ◽

Relative Standard ◽

Plasma Concentration Time Curve

To investigate the pharmacokinetics of 2, 3, 8-trimethylellagic (TMEA) in rats in vivo and determine the possible effects of the pathological conditions and compatibility, a rapid and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for quantitative determination was developed. TMEA and Artemetin (internal standard, IS) were separated on an Acquity Shim-pack GIST column with a total running time of 7 min using gradient elution at a flow rate of 0.3 mL/min. The intraday and interday relative standard deviations were <9.50%, and the relative error of accuracy was between −5.70% and 2.96%. The calibration curve of TMEA demonstrated good linearity with r2 = 0.9996, with the average recovery changing from 94.77% to 102.47% and the matrix effect from 93.16% to 100.15%. Compared with the normal group, the area under the plasma concentration-time curve from time 0 to the last time of quantifiable concentration (AUC(0 − t)), area under the plasma concentration-time curve from time 0 extrapolated to infinite time (AUC(0 − ∞)), and the maximum concentration (Cmax) of TMEA increased, whereas the time of maximum concentration (Tmax) and apparent clearance (CL/F) remarkably decreased in the TMEA group. With significantly reduced CL/F, AUC(0 − t), AUC(0 − ∞), and Cmax for TMEA were increased approximately one time after combining with 3, 7-Di-O-methylducheside A (DOMA). AUC(0 − t) and Cmax for TMEA in the 2, 3, 8-trimethylellagic-3, 8-dimethoxyellagic acid-2-oxyglucoside (TMEA-DMAG) group were significantly lower than that in the TMEA group with clearly prolonged Tmax and increased CL/F. These findings indicate that the changes in the pharmacokinetic parameters of TMEA may be caused by pathological and combination conditions.

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In Vivo Kinetics and Biotransformation of Aflatoxin B1 in Dairy Cows Based on the Establishment of a Reliable UHPLC-MS/MS Method

Frontiers in Chemistry ◽

10.3389/fchem.2021.809480 ◽

2021 ◽

Vol 9 ◽

Author(s):

Wenbo Guo ◽

Zhichen Fan ◽

Kai Fan ◽

Jiajia Meng ◽

Dongxia Nie ◽

...

Keyword(s):

Dairy Cows ◽

High Performance ◽

Life Time ◽

Limit Of Quantification ◽

Relative Standard ◽

Liquid Chromatography Tandem Mass ◽

Carry Over ◽

Dose Trial ◽

Aflatoxin B

The in vivo kinetics of aflatoxin B1 (AFB1) and its carry-over as aflatoxin M1 (AFM1) in milk as well as the toxin loads in the tissue of dairy cows were assessed through a repetitive feeding trial of an AFB1-contaminated diet of 4 μg kg−1 body weight (b.w.) for 13 days. This was followed by a clearance period that ended with a single dose trial of an AFB1-contaminated diet of 40 μg kg−1 b.w. An ultra-high performance liquid chromatography tandem mass spectrometry method was developed and successfully validated by the determination of linearity (R2 ≥ 0.990), sensitivity (lower limit of quantification, 0.1–0.2 ng ml−1), recovery (79.5–111.2%), and precision relative standard deviation (RSD) ≤14.7%) in plasma, milk, and various tissues. The repetitive ingestion of AFB1 indicated that the biotransformation of AFB1 to AFM1 occurred within 48 h, and the clearance period of AFM1 in milk was not more than 2 days. The carry-over rate of AFM1 in milk during the continuous ingestion experiment was in the range of 1.15–2.30% at a steady state. The in vivo kinetic results indicated that AFB1 reached a maximum concentration of 3.8 ± 0.9 ng ml−1 within 35.0 ± 10.2 min and was slowly eliminated from the plasma, with a half-life time (T1/2) of 931.1 ± 30.8 min. Meanwhile, AFM1 reached a plateau in plasma (0.5 ± 0.1 ng ml−1) at 4 h after the ingestion. AFB1 was found in the heart, spleen, lungs, and kidneys at concentrations of 1.6 ± 0.3, 4.1 ± 1.2, 3.3 ± 0.9 and 5.6 ± 1.4 μg kg−1, respectively. AFM1 was observed in the spleen and kidneys at concentrations of only 0.7 ± 0.2 and 0.8 ± 0.1 μg kg−1, respectively. In conclusion, the in vivo kinetics and biotransformation of AFB1 in dairy cows were determined using the developed UHPLC-MS/MS method, and the present findings could be helpful in assessing the health risks to consumers.

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Simultaneous determination of calycosin, prim-O-glucosylcimifugin, and paeoniflorin in rat plasma by HPLC-MS/MS: application in the pharmacokinetic analysis of HQCF

Journal of International Medical Research ◽

10.1177/0300060520972902 ◽

2020 ◽

Vol 48 (11) ◽

pp. 030006052097290

Author(s):

Yulong Gu ◽

Xianglan Piao ◽

Dan Zhu

Keyword(s):

Formic Acid ◽

High Performance ◽

Internal Standard ◽

Gradient Elution ◽

Rat Plasma ◽

Selected Reaction Monitoring ◽

Pharmacokinetic Analysis ◽

Ionization Source ◽

Liquid Chromatography Tandem Mass

Objective This study aimed to develop and validate a high-performance liquid chromatography–tandem mass spectrometry method to simultaneously determine three bioactive components of the Huangqi Chifeng decoction (HQCF) in rat plasma. Methods Taxol was used as an internal standard in the developed method. Chromatographic separation was performed on a C18 column using a gradient elution with 0.1% formic acid in acetonitrile (v/v) and 0.1% formic acid in water (v/v) as the mobile phases at a flow rate of 0.4 mL·minute−1. All compounds were monitored via selected reaction monitoring with an electrospray ionization source. Results The lower limits of quantification of paeoniflorin, calycosin, and prim- O-glucosylcimifugin were 15.0, 0.75, and 0.75 ng·mL−1, respectively. The calibration curves indicated optimal linearity ( r > 0.99) across the concentration ranges. The specificity, precision, accuracy, recovery, matrix effect, and stability of the method were validated. This method was successfully applied in a pharmacokinetics study of the three compounds in rat plasma. Conclusion The pharmacokinetics results provide insights into the mechanisms of HQCF in vivo and its future clinical application.

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A Validated HPLC-MS/MS Method for Simultaneous Determination of Militarine and Its Three Metabolites in Rat Plasma: Application to a Pharmacokinetic Study

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/2371784 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Hui-Yuan Sun ◽

Lin Zheng ◽

Zi-Peng Gong ◽

Yue-Ting Li ◽

Chang Yang ◽

...

Keyword(s):

Formic Acid ◽

Simultaneous Determination ◽

Multiple Reaction Monitoring ◽

Area Under The Curve ◽

Internal Standard ◽

Rat Plasma ◽

Relative Standard ◽

Method Accuracy

A rapid, reliable, and sensitive HPLC-electrospray ionization-tandem mass spectrometry (HPLC-MS/MS) method was established and validated for simultaneous determination of militarine and its three metabolites (gastrodin, α-isobutylmalic acid, and gymnoside I) in rat plasma. Plasma was acidified with formic acid, and protein was precipitated with methanol. MS/MS with ESI and multiple reaction monitoring at m/z 725.3→457.3, 457.1→127, 304.3→107.2, 189→129, and 417.1→267.1 was used for determination of militarine, gastrodin, α-isobutylmalic acid, gymnoside I, and puerarin (internal standard), respectively. Chromatographic separation was conducted using an ACE UltraCore SuperC18 (2.1 × 100 mm, 2.5 μm) column with gradient mobile phase (0.1% formic acid in water and acetonitrile). The lower limits of quantitation for militarine, gastrodin, α-isobutylmalic acid, and gymnoside I were 1.02, 2.96, 1.64, and 0.3 ng/mL, respectively. The relative standard deviations of intra- and interday measurements were less than 15%, and the method accuracy ranged from 87.4% to 112.5%. The extraction recovery was 83.52%-105.34%, and no matrix effect was observed. The three metabolites (gastrodin, α-isobutylmalic acid, and gymnoside I) were synchronously detected at 0.83 h, suggesting that militarine was rapidly transformed to gastrodin, α-isobutylmalic acid, and gymnoside I. Moreover, the area under the curve (AUC) and Cmax of militarine were significantly lower than those of gastrodin and α-isobutylmalic acid, showing that militarine was largely metabolized to gastrodin and α-isobutylmalic acid in vivo. The studies on pharmacokinetics of militarine and its three metabolites were of great use for facilitating the clinical application of militarine and were also highly meaningful for the potential development of militarine.

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An UPLC-MS/MS Method for Routine Quantification of Insulin Degludec in Plasma

Current Pharmaceutical Analysis ◽

10.2174/1573412915666190304145149 ◽

2020 ◽

Vol 16 (6) ◽

pp. 792-799

Author(s):

Yudong Zhang ◽

Yue Jiang ◽

Ya Wang ◽

Ling Wang ◽

Weijie Han ◽

...

Keyword(s):

Formic Acid ◽

Matrix Effects ◽

Multiple Reaction Monitoring ◽

Subcutaneous Administration ◽

Ultra Performance Liquid Chromatography ◽

Insulin Degludec ◽

Limit Of Quantification ◽

Relative Standard ◽

Liquid Chromatography Tandem Mass ◽

Acquity Uplc

Background: Chromatographic methods for determination of insulin degludec in rabbit plasma by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry were developed. Methods: Analytes were eluted from Waters ACQUITY UPLC® Peptide BEH C18 (2.1×50mm, 300Å) column with a mobile phase of water containing 0.1% formic acid (A) and acetonitrile containing 0.1% formic acid (B). Quantitation of insulin degludec was performed using 1222.06 > 641.24 m/z on Multiple- Reaction Monitoring (MRM) mode. Results: Good linearity was observed in the concentration range of 500-50000 ng/mL (r >0.99), and the lower limit of quantification was 500ng/mL. The within-run and between-run precision (expressed as relative standard deviation, RSD) of insulin degludec were ≤ 14.16% and ≤ 13.64% respectively, and the accuracy was within 94.37-96.35%. The recovery and matrix effects were both within acceptable limits. Conclusion: This method was successfully applied for the pharmacokinetic study of insulin degludec in rabbit after subcutaneous administration.

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Simultaneous Determination of Columbianadin and Its Metabolite Columbianetin in Rat Plasma by LC-MS/MS: Application to Pharmacokinetics of Columbianadin after Oral Administration

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/8568303 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Jin Li ◽

Zhen Li ◽

Qian Luo ◽

Chun-Peng Wang ◽

Jun He ◽

...

Keyword(s):

Oral Administration ◽

Internal Standard ◽

Rat Plasma ◽

Pharmacokinetic Parameters ◽

Antitumor Activities ◽

Limit Of Quantification ◽

Potential Development ◽

Liquid Chromatography Tandem Mass ◽

Acetate Aqueous Solution

Columbianadin and its metabolite columbianetin exhibited the anti-inflammatory, analgesic, calcium channel blocking and antitumor activities. To compare the differences between pharmacokinetics of columbianadin and its metabolite columbianetin after oral administration of pure columbianadin and Angelicae Pubescentis Radix (APR) extract, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established and validated to simultaneously determine columbianadin and columbianetin in rat plasma. Two analytes and an internal standard (warfarin) were well separated and determined after liquid-liquid extraction with ethyl acetate. Ammonium acetate aqueous solution (1 mmol/L) and acetonitrile were used as the mobile phase and the flow rate was 0.3 mL/min. The lower limit of quantification (LLOQ) was 0.1 ng/mL for columbianetin and 0.5 ng/mL for columbianadin, respectively. There were significant differences between some pharmacokinetic parameters and bioavailability of columbianadin after oral administration of pure columbianadin and APR extract. The studies on comparative pharmacokinetics of columbianadin were of great use for facilitating the clinical application of columbianadin and were also highly meaningful for the potential development of APR.

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Factorial Design Optimisation of Solid Phase Extraction for Preconcentration of Parabens in Wastewater Using Ultra-High Performance Liquid Chromatography Triple Quadrupole Mass Spectrometry

Current Analytical Chemistry ◽

10.2174/1573411014666180627150854 ◽

2020 ◽

Vol 16 (4) ◽

pp. 436-446

Author(s):

Vallerie A. Muckoya ◽

Philiswa N. Nomngongo ◽

Jane C. Ngila

Keyword(s):

Solid Phase Extraction ◽

Formic Acid ◽

Factorial Design ◽

Solid Phase ◽

Treatment Plant ◽

Phase Extraction ◽

Limit Of Quantification ◽

Analytical Technique ◽

Relative Standard ◽

Simulated Wastewater

Background: Parabens are synthetic esters used extensively as preservatives and/or bactericides in personal care personal products. Objective: Development and validation of a novel robust chemometric assisted analytical technique with superior analytical performances for the determination of ethylparaben, methylparaben and propylparaben, using simulated wastewater matrix. Methods: An automated Solid Phase Extraction (SPE) method coupled with liquid chromatographymass spectrometry was applied in this study. A gradient elution programme comprising of 0.1% formic acid in deionised water (A) and 0.1% formic acid in Methanol (B) was employed on a 100 x 2.1 mm, 3.0 μm a particle size biphenyl column. Two-level (2k) full factorial design coupled with response surface methodology was used for optimisation and investigation of SPE experimental variables that had the most significant outcome of the analytical response. Results: According to the analysis of variance (ANOVA), sample pH and eluent volume were statistically the most significant parameters. The method developed was validated for accuracy, precision, Limits of Detection (LOD) and Limit of Quantification (LOQ) and linearity. The LOD and LOQ established under those optimised conditions varied between 0.04-0.12 μgL−1 and 0.14-0.40 μgL−1 respectively. The use of matrix-matched external calibration provided extraction recoveries between 78-128% with relative standard deviations at 2-11% for two spike levels (10 and 100 μgL-1) in three different water matrices (simulated wastewater, influent and effluent water). Conclusion: The newly developed method was applied successfully to the analyses of parabens in wastewater samples at different sampling points of a wastewater treatment plant, revealing concentrations of up to 3 μgL−1.

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Development and Validation of a New Method for the Determination of Anti-hepatitis C Agent Simeprevir in Human Plasma using HPLC with Fluorescence Detection

Current Analytical Chemistry ◽

10.2174/1573411015666181217121619 ◽

2020 ◽

Vol 16 (4) ◽

pp. 428-435

Author(s):

Ahmed F.A. Youssef ◽

Yousry M. Issa ◽

Kareem M. Nabil

Keyword(s):

Hepatitis C ◽

Human Plasma ◽

Fluorescence Detection ◽

Internal Standard ◽

Protein Precipitation ◽

Assay Method ◽

Fluorescence Detector ◽

Limit Of Quantification ◽

Relative Standard

Background: Simeprevir is one of the recently discovered drugs for treating hepatitis C which is one of the major diseases across the globe. Objective: The present study involves the development of a new and unique High-Performance Liquid Chromatography (HPLC) method using fluorescence detection for the determination of simeprevir (SIM) in human plasma. Methods: Two methods of extractions were tested, protein precipitation using acetonitrile and liquidliquid extraction. A 25 mM dipotassium hydrogen orthophosphate (pH 7.0)/ACN (50/50; v/v), was used as mobile phase and C18 reversed phase column as the stationary phase. The chromatographic conditions were optimized and the concentration of simeprevir was determined by using the fluorescence detector. Cyclobenzaprine was used as an internal standard. Results: Recovery of the assay method based on protein precipitation was up to 100%. Intra-day and inter-day accuracies range from 92.30 to 107.80%, with Relative Standard Deviation (RSD) range 1.65-8.02%. The present method was successfully applied to a pharmacokinetic study where SIM was administered as a single dose of 150 mg SIM/capsule (Olysio®) to healthy individuals. Conclusion: This method exhibits high sensitivity with a low limit of quantification 10 ng mL-1, good selectivity using fluorescence detection, wide linear application range 10-3000 ng mL-1, good recovery and highly precise and validation results. The developed method can be applied in routine analysis for real samples.

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High-Performance Liquid Chromatography-Tandem Mass Spectrometry for Buprenorphine Evaluation in Plasma—Application to Pharmacokinetic Studies in Rabbits

Molecules ◽

10.3390/molecules26020437 ◽

2021 ◽

Vol 26 (2) ◽

pp. 437

Author(s):

Marta Tikhomirov ◽

Błażej Poźniak ◽

Tomasz Śniegocki

Keyword(s):

High Performance ◽

Pharmacokinetic Profile ◽

Pharmacokinetic Studies ◽

Limit Of Quantification ◽

Reliable Determination ◽

Main Challenge ◽

Analytical Protocol ◽

Liquid Chromatography Tandem Mass ◽

Cost Efficient

The precise and reliable determination of buprenorphine concentration is fundamental in certain medical or research applications, particularly in pharmacokinetic studies of this opioid. The main challenge is, however, the development of an analytical method that is sensitive enough, as the detected in vivo concentrations often fall in very low ranges. Thus, in this study we aimed at developing a sensitive, repeatable, cost-efficient, and easy HPLC analytical protocol for buprenorphine in rabbit plasma. In order to obtain this, the HPLC-MS2 system was used to elaborate and validate the method for samples purified with liquid-liquid extraction. Fragment ions 468.6→396.2 and 468.6→414.2 were monitored, and the method resulted in a high repeatability and reproducibility and a limit of quantification of 0.25 µg/L with a recovery of 98.7–109.0%. The method was linear in a range of 0.25–2000 µg/L. The suitability of the analytical procedure was tested in rabbits in a pilot pharmacokinetic study, and it was revealed that the method was suitable for comprehensively describing the pharmacokinetic profile after buprenorphine intravenous administration at a dose of 300 µg/kg. Thus, the method suitability for pharmacokinetic application was confirmed by both the good validation results of the method and successful in vivo tests in rabbits.

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