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

Molecules ◽  
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.

scholarly journals An LC-MS/MS Method for Simultaneous Determination of the Toxic and Active Components of Cortex Periplocae in Rat Plasma and Application to a Pharmacokinetic Study

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Zhen Li ◽  
Yang Li ◽  
Jin Li ◽  
Rui Liu ◽  
Jia Hao ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Simple Liquid ◽  
Active Components ◽  
Limit Of Quantification ◽  
Liquid Chromatography Tandem Mass

A sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the toxic and other active components including isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract to rats. Plasma samples were prepared by protein precipitation with methanol. All compounds were separated on a C18 column with gradient elution using acetonitrile and formic acid aqueous solution (0.1%, v/v) as the mobile phase at a flow rate of 0.3 mL/min. The detection of all compounds was accomplished by multiple-reaction monitoring (MRM) in the positive electrospray ionization mode. The LC-MS/MS method exhibited good linearity for five analytes. The lower limit of quantification (LLOQ) was 0.48 ng/mL for scopoletin, periplogenin, and periplocymarin; 2.4 ng/mL for isovanillin and periplocin. The extraction recoveries of all compounds were more than 90% and the RSDs were below 10%. It was found that the absorption of scopoletin and periplocin was rapid in vivo after oral administration of cortex periplocae extract. Furthermore, periplocymarin possessed abundant plasma exposure. The results demonstrated that the validated method was efficiently applied for the pharmacokinetic studies of isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract.

scholarly journals FORMULATION AND PHARMACOKINETIC DETERMINATION OF GALLIC ACID IN EMBLICA OFFICINALIS

2017 ◽  
Vol 9 (5) ◽  
pp. 9 ◽  
Author(s):  
Sangeetha S. ◽  
Malay K. Samanta ◽  
Kavitha R. ◽  
Remya P. N. ◽  
Saraswathi T.
Keyword(s):  
Gallic Acid ◽  
High Performance ◽  
Pharmacokinetic Profile ◽  
Pure Form ◽  
P Value ◽  
Pharmacokinetic Studies ◽  
Pharmacokinetic Data ◽  
Emblica Officinalis ◽  
Compression Technique

Objective: The present work was to formulate oral herbal tablets of Emblica officinalis extract and also with pure gallic acid, further to determine the dosage frequency through pharmacokinetic profiles obtained for the same.Methods: The Emblica officinalis fruits were suitably extracted and the concentration of gallic acid in Emblica officinalis extract was estimated by HPTLC (High-Performance Thin Layer Chromatography) with a comparison to pure form. Tablets were prepared with extract and synthetic form through direct compression technique by varying the process and formulation parameters. The formulated tablets were administered to rabbit models and their pharmacokinetic profile was studied after withdrawing blood samples through HPLC (High-Performance Liquid Chromatography).Results: The concentration of gallic acid in Emblica officinalis was found to be 8.21%. The pre and post compression parameters evaluated for the formulated batches found to be within the pharmacopoeial limits. The in vivo pharmacokinetic studies conducted in rabbit models showed that there were no significant differences with p-value between the pharmacokinetic data obtained for pure and extract gallic acid tablets. The Cmax was found to be 4.59±0.95 µg/ml in the extract form which was little low when compared to the pure form of 6.38±1.08 µg/ml. The t1/2 in the extract form was 6.0±0.33 h, whereas it was 4.92±0.36 h in the pure form of gallic acid.Conclusion: The Emblica officinalis extract tablet showed average t1/2 of 6 h, so about every 6 h one tablet compared to 4 h of t1/2 for pure gallic acid tablet can be the dosing frequency for the rabbit. 

scholarly journals Comparative Studies on Multi-Component Pharmacokinetics of Polygonum multiflorum Thunb Extract After Oral Administration in Different Rat Models

2021 ◽  
Vol 12 ◽  
Author(s):  
Ninghui Ma ◽  
Yong Zhang ◽  
Liyan Sun ◽  
Yuan Zhao ◽  
Yue Ding ◽  
...  
Keyword(s):  
Phase Ii ◽  
High Performance ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Polygonum Multiflorum ◽  
Liquid Chromatography Tandem Mass ◽  
Aloe Emodin ◽  
Main Basis ◽  
Phase Ii Metabolites

The clinical use of Polygonum multiflorum Thunb (PM) has been restricted or banned in many countries, due to its hepatotoxic adverse effects. Its toxicity research has become a hot topic. So far, the pharmacokinetic studies of PM, focusing on prototype compounds such as 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), emodin, and physcion, have been considered the main basis of pharmacodynamic material or of toxic effect. However, pharmacokinetic studies of its phase II metabolites have not yet been reported, mainly because the quantifications of such metabolites are difficult to do without the reference substance. In addition, pharmacokinetic studies on different pathological models treated with PM have also not been reported. On the other hand, toxic effects of PM have been reported in patients diagnosed with different liver pathologies. In the present work, a simultaneous quantitation method for eight prototypes components of PM and their five phase II metabolites has been performed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and used for the pharmacokinetic study of PM in two different liver pathological models in rats (normal, alpha-naphthylisothiocyanate (ANIT), and carbon tetrachloride (CCl4)). The results showed that the main blood-entering components of PM are TSG, emodin, physcion, emodin-8-O-β⁃D⁃glucoside (E-Glu), physcion-8-O-β⁃D⁃glucoside (P-Glu), aloe-emodin, gallic acid, resveratrol and catechin, among which TSG, emodin, and catechin were primary metabolized in phase II, while resveratrol was converted to all phase II metabolites, and the others were metabolized as drug prototypes. Meanwhile, their pharmacokinetic parameters in the different models also exhibited significant differences. For instance, the AUC (0-∞) values of the TSG prototype and its phase II metabolites were higher in the ANIT group, followed by CCl4 group and the normal group, while the AUC (0-∞) values of the emodin prototype and its phase II metabolites were higher in the CCl4 group. To further illustrate the reasons for the pharmacokinetic differences, bilirubin metabolizing enzymes and transporters in the liver were measured, and the correlations with the AUC of the main compounds were analyzed. TSG and aloe-emodin have significant negative correlations with UGT1A1, BSEP, OATP1A4, OCT1, NTCP, MRP2 and MDR1 (p < 0.01). These data suggest that when the expression of metabolic enzymes and transporters in the liver is inhibited, the exposure levels of some components of PM might be promoted in vivo.

scholarly journals PHARMACOKINETIC PROFILE OF 75 MG CLOPIDOGREL IN PLASMA OF INDONESIAN HEALTHY SUBJECTS BY ULTRA HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY

2018 ◽  
Vol 10 (1) ◽  
pp. 331
Author(s):  
Yahdiana Harahap ◽  
Ganesya Rita Putri ◽  
Herman Suryadi
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Maximum Concentration ◽  
Healthy Subjects ◽  
High Performance ◽  
Pharmacokinetic Profile ◽  
Tandem Mass ◽  
Linear Calibration ◽  
Liquid Chromatography Tandem Mass

Objective: This study aimed to determine clopidogrel in plasma to obtain its pharmacokinetic profile using ultra-high-performance liquidchromatography-tandem mass spectrometry (UPLC-MS/MS).Methods: Clopidogrel analysis was performed in vivo by UPLC-MS/MS using validated methods. Subjects received 75 mg clopidogrel, and plasmasamples were collected at 14 time points after 0 baseline (pre-dose): 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 8, 12, 18, and 24 h.Results: A linear calibration curve was produced in the range of 20–5.000 pg/mL. This method fulfills the criteria for validation according to theEuropean Medicines Agency guidelines. The obtained pharmacokinetic profile of clopidogrel was as follows: Maximum concentration=1.146 ng/mL,time at maximum concentration (tmax)=1 h, half-life (t½)=7.01 h, area under curve (AUC)0−t=7.420 ng h/mL, and AUC0−t=8.111 ng h/mL.Conclusion: Clopidogrel analysis using a UPLC/MS-MS system with liquid-liquid extraction method was successfully conducted using plasma samplesfrom three healthy subjects who administered 75 mg of clopidogrel tablet.

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

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.

scholarly journals Investigation of In Vivo and In Vitro Pharmacokinetic Characteristics of Kaji-ichigoside F1 in Rats

2020 ◽  
Vol 15 (3) ◽  
pp. 1934578X2091501
Author(s):  
Wenjuan Cui ◽  
Xiaoguang Fan ◽  
Naizhi Wang ◽  
Zhikun Zhang ◽  
Zhaolong Zhang ◽  
...  
Keyword(s):  
High Performance ◽  
Single Step ◽  
Selected Reaction Monitoring ◽  
Pharmacokinetic Studies ◽  
Triterpenoid Saponin ◽  
Pentacyclic Triterpenoid ◽  
Validation Parameters ◽  
Liquid Chromatography Tandem Mass

Kaji-ichigoside F1, a pentacyclic triterpenoid saponin, exhibits various beneficial pharmacological effects. In this study, a simple, rapid, and specific high-performance liquid chromatography-tandem mass spectrometry method for rapid quantification of kaji-ichigoside F1 in rat biological matrix was developed. Plasma was prepared by a single-step protein precipitation followed by separation of the analyte using an Inertsil ODS-3 column with a gradient mobile phase. Positive ion electrospray was used and selected reaction monitoring transitions were m/ z 673.27 → 511.15 for kaji-ichigoside F1 and m/ z 429.19 → 267.29 for morroniside, respectively. The developed method was validated with linear range of 20 to 10 000 ng/mL. All validation parameters were well within the acceptance limit based on the guidance of FDA. The validated method was successfully applied to analyze samples from the in vivo and in vitro pharmacokinetic studies in rats.

scholarly journals Analysis of the Carry-Over of Ochratoxin A from Feed to Milk, Blood, Urine, and Different Tissues of Dairy Cows Based on the Establishment of a Reliable LC-MS/MS Method

Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2823 ◽  
Author(s):  
Zhiqi Zhang ◽  
Zhichen Fan ◽  
Dongxia Nie ◽  
Zhihui Zhao ◽  
Zheng Han
Keyword(s):  
Dairy Cows ◽  
Ochratoxin A ◽  
Limit Of Quantification ◽  
Fresh Milk ◽  
Liquid Chromatography Tandem Mass ◽  
Ochratoxin Α ◽  
Carry Over ◽  
First Time ◽  
Different Tissues

A rapid and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous determination of ochratoxin A (OTA) and its metabolite ochratoxin α (OTα), for the first time, in dairy cow plasma, milk, urine, heart, liver, spleen, lung, and kidney. The established method was extensively validated by determining the linearity (R2 ≥ 0.990), sensitivity (lower limit of quantification, 0.1–0.2 ng mL−1), recovery (75.3–114.1%), precision (RSD ≤ 13.6%), and stability (≥83.0%). Based on the methodological advances, the carry-over of OTA was subsequently studied after oral administration of 30 μg/kg body weight OTA to dairy cows. As revealed, OTA and OTα were detected in urine, with maximal concentrations of 1.8 ng mL−1 and 324.6 ng mL−1, respectively, but not in milk, plasma, or different tissues, verifying the protection effects of rumen flora against OTA exposure for dairy cows. Moreover, 100 fresh milk samples randomly collected from different supermarkets in Shanghai were also analyzed, and no positive samples were found, further proving the correctness of the in vivo biotransformation results. Thus, from the currently available data, regarding OTA contamination issues on dairy cows, no significant health risks were related to OTA exposure due to the consumption of these products.

scholarly journals Simultaneous quantification of cortisol and cortisone in serums and saliva from depressive patients by supported liquid extraction coupled to HPLC–MS/MSs

2020 ◽  
Vol 32 (4) ◽  
pp. 269-275
Author(s):  
Binbin Chen ◽  
Haiyan Lyu ◽  
Xiangzhen Xu ◽  
Chen Wang
Keyword(s):  
High Performance ◽  
Depressive Disorders ◽  
Liquid Extraction ◽  
Butyl Ether ◽  
Limit Of Quantification ◽  
Regulatory Guidance ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Efficient Extraction ◽  
Depressive Patients

Cortisol and cortisone are 2 important glucocorticoids produced in the human hypothalamus–pituitary–adrenal (HPA) axis that respond to stress. An analytical method to determinate cortisol and cortisone in serum and saliva using high-performance liquid chromatography–tandem mass spectrometry following a supported liquid extraction (SLE) was developed. Serum and saliva samples of 0.2 mL were extracted by SLE three times using 0.4 mL of methyl tert-butyl ether each time. The chromatographic separation was obtained on an Agilent Poroshell column using a 0.01% formic acid buffer and acetonitrile (60:40, v/v) as the solvent with a flow rate of 0.3 mL/min. Optimized quantitative mass transitions for cortisol, cortisone, and cortisone d-4 were 363.2/121.0 (m/z), 361.2/163.1 (m/z), and 367.1/270.7 (m/z), respectively. The method validation was achieved according to regulatory guidance. The lower limit of quantification (LLOQ) in serum were 2 ng/mL for cortisol and 1 ng/mL for cortisone, and the LLOQ in saliva were 0.1 ng/mL for cortisol and 0.2 ng/mL for cortisone. The developed method showed convenient and efficient extraction, a lower LLOQ, and a short running time. Modest correlations between serum and saliva cortisol and cortisone concentrations were found. The method was successfully applied in assessing the HPA condition of patients with depressive disorders.

scholarly journals Percutaneous Microdialysis and Pharmacokinetic Study of Tongluo-Qutong Rubber Plaster in Rats by UPLC-MS/MS

2020 ◽  
Vol 15 (9) ◽  
pp. 1934578X2095782
Author(s):  
Jiaxin Pi ◽  
Ying Zhang ◽  
Xutong Ma ◽  
Ping Wang ◽  
Wei Xiong ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Pharmacokinetic Studies ◽  
Active Ingredients ◽  
Time Curve ◽  
Liquid Chromatography Tandem Mass ◽  
Medicine Prescription ◽  
The Mean ◽  
Microdialysis Study ◽  
Dermal Administration

Tongluo-Qutong rubber plaster (TQRP) is a well-known traditional Chinese medicine prescription for the treatment of osteoarthritis and cervical spondylosis. Due to a lack of in vivo permeation data, the active ingredients of TQRP have not been fully elucidated, presenting a huge obstacle to quality evaluation, pharmacokinetic studies, and safety assessment of TQRP for clinical application. In this study, a selective and reproducible ultraperformance liquid chromatography tandem mass spectrometry method was developed and validated for percutaneous microdialysis and pharmacokinetic experiments. In the percutaneous microdialysis study, the mean area under the concentration–time curve (AUC0-24h) of emodin (EMO) and piperine (PIP) were 127.1 and 2603.6 h·ng/mL, respectively. In the pharmacokinetic study, ferulic acid (FA), EMO, and PIP were determined in plasma samples. The mean AUC0-32h values of FA, EMO, and PIP in plasma were 15441.5, 202.0, and 1704.5 h·ng/mL, respectively. The in vivo exposure levels of active ingredients such as FA, EMO, and PIP after dermal administration of TQRP provide insights and data to support identification of its bioactive components and further study of its mechanism of action.

scholarly journals Isofraxidin: Synthesis, Biosynthesis, Isolation, Pharmacokinetic and Pharmacological Properties

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2040 ◽  
Author(s):  
Mohammad Bagher Majnooni ◽  
Sajad Fakhri ◽  
Yalda Shokoohinia ◽  
Mahdi Mojarrab ◽  
Sara Kazemi-Afrakoti ◽  
...  
Keyword(s):  
Heart Diseases ◽  
Pharmacokinetic Profile ◽  
Extraction Methods ◽  
Point Of View ◽  
Pharmacokinetic Studies ◽  
Pharmacological Properties ◽  
Neuroprotective Effects ◽  
Hydroxy Coumarin ◽  
Factor Α

Isofraxidin (7-hydroxy-6, 8-dimethoxy coumarin) (IF) is a hydroxy coumarin with several biological and pharmacological activities. The plant kingdom is of the most prominent sources of IF, which, among them, Eleutherococcus and Fraxinus are the well-known genera in which IF could be isolated/extracted from their species. Considering the complex pathophysiological mechanisms behind some diseases (e.g., cancer, neurodegenerative diseases, and heart diseases), introducing IF as a potent multi-target agent, which possesses several herbal sources and the multiple methods for isolation/purification/synthesis, along with the unique pharmacokinetic profile and low levels of side effects, could be of great importance. Accordingly, a comprehensive review was done without time limitations until February 2020. IF extraction methods include microwave, mechanochemical, and ultrasound, along with other conventional methods in the presence of semi-polar solvents such as ethyl acetate (EtOAc). In addition to the isolation methods, related synthesis protocols of IF is also of great importance. From the synthesis point of view, benzaldehyde derivatives are widely used as precursors for IF synthesis. Along with the methods of isolation and biosynthesis, IF pharmacokinetic studies showed hopeful in vivo results of its rapid absorption after oral uses, leading to different pharmacological effects. In this regard, IF targets varieties of inflammatory mediators including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-α (TNF-α), and matrix metalloproteinases (MMPs). thereby indicating anticancer, cardioprotective, and neuroprotective effects. This is the first review on the synthesis, biosynthesis, isolation, and pharmacokinetic and pharmacological properties of IF in combating different diseases.

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