Pharmacokinetics Study of Rabdosia Rubescens Drop Pills Based on UPLC-MS/MS

2021 ◽  
Vol 18 ◽  
Author(s):  
Xi-Yu Wei ◽  
Zhen-Zhen Zhang ◽  
Tao Xie ◽  
Yue-Sheng Xie ◽  
Yue Sun ◽  
...  
Keyword(s):  
Rosmarinic Acid ◽  
Mobile Phase ◽  
Multiple Reaction Monitoring ◽  
Dose Range ◽  
Rat Plasma ◽  
Negative Ion ◽  
Intragastric Administration ◽  
Pharmacokinetic Studies ◽  
Significant Difference ◽  
Rabdosia Rubescens

Background: Rabdosia rubescens drop pills have the effects of clearing away heat and toxin, detumescence, relieving pain. Objective: A simple and sensitive method for simultaneous determination of oridonin, ponicidin, and rosmarinic acid in rat plasma was developed based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Methods: Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C18 column (2.1 × 100 mm, 1.7 µm) with a mobile phase consisting of water containing 0.2% formic acid (mobile phase A) and methanol (mobile phase B) at a flow rate of 0.3 mL/min over a total run time of 3.8 min. All analytes were measured with optimized multiple reaction monitoring (MRM) in positive and negative ion ESI mode. Results: The transitions of oridonin, ponicidin, rosmarinic acid, diphenhydramine, and chloramphenicol were 365.3→347.3, 363.3→345.2, 359.0→160.9, 256.0→167.2, and 321.1→151.9, respectively. The linear ranges were 1-256 ng/mL for ponicidin and rosmarinic acid and 2-512 ng/mL for oridonin. The validated method wasstable and reliable. There was no significant difference in the half-life (t1/2) of the three analytes at three doses. The area under the curve (AUC0-t) and peak concentration (Cmax) of the three analytes decreased linearly in each dose range, and the linear correlation R2 of each analyte under the three doses was greater than 0.95. Conclusion: This method was successfully applied to pharmacokinetic studies of oridonin, ponicidin, and rosmarinic acid in rat plasma after intragastric administration of Rabdosia rubescens drop pills.

A Sensitive UPLC-MS/MS Method for the Determination of Flurbiprofen in Rat Plasma: Application to Real Sample

2021 ◽  
Author(s):  
Mehmet Emrah Yaman ◽  
Alptug Atila ◽  
Tugrul Cagri Akman ◽  
Mevlut Albayrak ◽  
Yucel Kadioglu ◽  
...  
Keyword(s):  
Retention Time ◽  
Mobile Phase ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
High Sensitivity ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Negative Ion ◽  
Linear Calibration ◽  
Multiple Reaction Monitoring Mode

Abstract For the quantification of flurbiprofen in rat plasma, a simple UPLC-MS/MS method with high sensitivity and short retention time for flurbiprofen was developed and validated using specific parameters. Etodolac was used as internal standard. The transitions (precursor to the product) of flurbiprofen and internal standard were obtained using the electrospray ionization in the negative ion multiple reaction monitoring mode, 243.2 → 199.2, 286.2 → 212.1, respectively. For chromatographic separation, C18 column was used for the stationary phase and gradient elution was used for the mobile phase. This mobile phase consisted of a methanol (A) and a 5 mM ammonium formate solution (B), which varied at a flow rate of 0.4 mL/min. For flurbiprofen, LLOQ was determined as 5 ng/mL. Quantification of flurbiprofen in the rat plasma with a linear calibration curve of 5–5000 ng/mL (r > 0.9991 for plasma) is possible with a retention time of 1.89 min. The total analysis time of the method was 3 min. The proposed method was validated. The intraday and inter-day precision (RSD%) and accuracy (RE%) were within 10% in all cases for flurbiprofen. The stability of flurbiprofen was evaluated under conditions such as short-term, long-term, autosampler and freeze/thaw. After method validation, flurbiprofen was succesfully quantified in real rat plasma samples.

A UPLC-MS/MS Method for Simultaneous Determination of Six Bioactive Compounds in Rat Plasma, and its Application to Pharmacokinetic Studies of Naoshuantong Granule in Rats

2019 ◽  
Vol 15 (3) ◽  
pp. 231-242
Author(s):  
Ping Wang ◽  
Shenmeng Jiang ◽  
Yu Zhao ◽  
Shuo Sun ◽  
Xiaoli Wen ◽  
...  
Keyword(s):  
Simultaneous Determination ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Negative Ion ◽  
Pharmacokinetic Studies ◽  
Acquity Uplc

Background: It is urgently needed to clarify the pharmacokinetic mechanism for the multibioactive constituents in Traditional Chinese Medicines for its clinical applications. A rapid, sensitive and reliable ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of Danshensu, Ferulic acid, Astragaloside IV, Naringin, Neohesperidin and Puerarin after oral administration of Naoshuantong Granule using Carbamazepine as internal standard (IS). Methods: The plasma samples were pretreated by liquid-liquid extraction method using ethyl acetate after acidification, and separated on a Waters ACQUITY UPLC® BEH C18 column (50×2.1 mm, i.d., 1.7 µm) by gradient elution with a mobile phase composing of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.2 mL/min. Multiple reaction monitoring (MRM) mode with both positive and negative ion mode was operated using an electrospray ionization (ESI) to detect the six compounds. Result: All calibration curves showed good linearity (r>0.99) over a wide concentration range. The intra- and inter-day precision (RSD%) was below 8.4% and the accuracy (RE%) ranged from 91.1% to 107.5%. The extraction recoveries of the six analytes and IS in the plasma were more than 77.9% and no severe matrix effect was observed. Conclusion: The fully validated method was successfully applied to the pharmacokinetics of Naoshuantong Granule.

scholarly journals Simultaneous Quantification of Four Phenylethanoid Glycosides in Rat Plasma by UPLC-MS/MS and Its Application to a Pharmacokinetic Study of Acanthus Ilicifolius Herb

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3117 ◽  
Author(s):  
Mengqi Zhang ◽  
Xia Ren ◽  
Shijun Yue ◽  
Qing Zhao ◽  
Changlun Shao ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Multiple Reaction Monitoring ◽  
Folk Medicine ◽  
Ethanol Extract ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Molecular Structures ◽  
Intragastric Administration ◽  
Phenylethanoid Glycosides ◽  
Acanthus Ilicifolius

Acanthus ilicifolius herb (AIH), the dry plant of Acanthus ilicifolius L., has long been used as a folk medicine for treating acute and chronic hepatitis. Phenylethanoid glycosides (PhGs) are one family of the main components in AIH with hepatoprotective, antioxidant, and anti-inflammatory activities. In this study, the pharmacokinetics of AIH was investigated preliminarily by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS). A simultaneously quantitative determination method for four PhGs (acteoside, isoacteoside, martynoside, and crenatoside) in rat plasma was first established by UPLC-MS/MS. These four PhGs were separated with an ACQUITY UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm) by gradient elution (mobile phase: MeCN and 0.1% formic acid in water, 0.4 mL/min). The mass spectrometry detection was performed using negative electrospray ionization (ESI−) in multiple reaction monitoring (MRM) mode. By the established method, the preliminary pharmacokinetics of AIH was elucidated using the kinetic parameters of the four PhGs in rat plasma after intragastric administration of AIH ethanol extract. All four PhGs showed double peaks on concentration-time curves, approximately at 0.5 h and 6 h, respectively. Their elimination half-lives (t1/2) were different, ranging from 3.42 h to 8.99 h, although they shared similar molecular structures. This work may provide a basis for the elucidation of the pharmacokinetic characteristics of bioactive components from AIH.

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 Comparative Pharmacokinetic Studies of Four Ginsenosides in Rat Plasma by UPLC-MS/MS after Oral Administration of Panax quinquefolius-Acorus gramineus and Panax quinquefolius Extracts

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Hailong Xie ◽  
Dongxue Wang ◽  
Wenjun Zhang ◽  
Xinjia Yan ◽  
Ying Zhao
Keyword(s):  
Oral Administration ◽  
Solid Phase ◽  
Multiple Reaction Monitoring ◽  
Critical Role ◽  
Extraction Procedure ◽  
Rat Plasma ◽  
Panax Quinquefolius ◽  
Pharmacokinetic Studies ◽  
Age Related ◽  
Acorus Gramineus

Panax quinquefolius (PQ) and Acorus gramineus (AG) are drug target pairs in traditional Chinese medicine (TCM), which are used to treat age-related diseases. In the present study, we simultaneously determined the contents of four main bioactive ginsenosides (Rb1, Rb2, Rd, and Re) in rat plasma using an ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Plasma specimens were purified by using the solid-phase extraction procedure, and separation was performed on Waters ACQUITY UPLC BEH C18 (100 mm × 2.1 mm, 1.7 μm) in multiple reaction monitoring (MRM) mode and negative electrospray ionization (ESI) mode. The established UPLC-MS/MS method showed good linear correlation (r ≥ 0.9978), stability (−11.93 to 12.11%), precision (RSD < 14.63%), and recovery (76.43%–95.20%). The lower limit of quantification was 3.6 ng/mL for Rb1, 1.6 ng/mL for Rb2, 1.2 ng/mL for Rd, and 2.5 ng/mL for Re. This validated method was successfully employed to investigate the pharmacokinetics of the four ginsenosides in rat plasma after oral administration of PQ-AG and PQ extracts. The results revealed the pharmacokinetic profiles of PQ-AG drug pair and clarified that AG played a critical role in stimulating the absorption of active ginsenosides in PQ. Collectively, our findings provided valid and reliable evidence for the rational use of PQ-AG in clinical practice.

Pharmacokinetics of Picroside I, II, III, IV in Rat Plasma by UPLCMS/ MS

2020 ◽  
Vol 16 (4) ◽  
pp. 438-445 ◽  
Author(s):  
Haili Xie ◽  
Xiaojie Lu ◽  
Weiqiang Jin ◽  
Hua Zhou ◽  
Dongxin Chen ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Negative Ion ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Picroside Ii ◽  
Bone Injury

Background: Modern pharmacological studies show that rhizoma coptidis has protective effects on the liver, gallbladder, kidney, cerebral ischemia-reperfusion, local hypoxia injury, antiinflammatory, bone injury, nerve cells and myocardial cells. The effective components have been isolated from picroside I, II, III and IV. Introduction: A selective and sensitive ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed for the simultaneous quantitative determination of picroside I, II, III and IV in rat plasma to aid the pharmacokinetics studies. Method: Sprague-Dawley (SD) rats were orally administered with 10 mg/kg, intravenously injected with 1 mg/kg for the mixture of picroside I, II, III and IV. The biological samples were collected at 0.083 3 h, 0.25 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h. A UPLC BEH C18 column (2.1 mm×50 mm, 1.7 μm) was used for chromatographic separation with the mobile phase consisting of acetonitrile and 0.1% formic acid by gradient elution. The flow rate was 0.4 mL/min. Multiple reaction monitoring (MRM) transitions were m/z 491.1→147.1 for picroside I, m/z 511.1→234.9 for picroside II, m/z 537.3→174.8 for picroside III and m/z 507.3→163.1 for picroside IV in negative ion mode. Result: The inter-day precision was less than 13%, the intra-day precision was less than 15%. The accuracy ranged from 89.4% to 111.1%. Recovery was higher than 79.1%, and the matrix effect ranged from 96.2% to 109.0%. Conclusion: The sensitive, rapid and selective UPLC-MS/MS method can be applied to the pharmacokinetic study of picroside I, II, III and IV in rats.

Development and Validation of a Method for Simultaneous Estimation of Sitagliptin and Ertugliflozin in Rat Plasma by LC–MS method

2020 ◽  
Vol 16 ◽  
Author(s):  
P. Venkateswara Rao ◽  
A. Lakshmana Rao ◽  
S.V.U.M. Prasad
Keyword(s):  
Matrix Effect ◽  
Multiple Reaction Monitoring ◽  
Rat Plasma ◽  
Marketing Approval ◽  
Simultaneous Estimation ◽  
Pharmacokinetic Studies ◽  
Oral Antidiabetic Agents ◽  
Liquid Liquid Extraction ◽  
Positive Mode ◽  
Development And Validation

Background: The development of sound bioanalytical LC-MS (liquid chromatography-mass spectroscopy) method(s) is of paramount importance during the process of drug discovery, development and culminating in a marketing approval. The use of oral antidiabetic agents has been increased significantly from last decades and till now no bioanalytical method is available for quantitation of sitagliptin (SG) and ertugliflozin (EG) in biological matrix which can be applied to pharmacokinetic studies using LC-MS/MS. Objective: To develop a new, rapid and sensitive LC–MS/MS method for the simultaneous estimation of sitagliptin (SG) and ertugliflozin (EG) in rat plasma by liquid–liquid extraction method (LLE) using deutereated sitagliptin (SGd6) and ertugliflozin (EGd6). Method: Chromatographic separation was carried out on a reverse phase Waters, Xetrra C18 (150mm x 4.6mm, 2μm) column using mixture of acetonitrile and OPA buffer (50:50v/v) at a flow rate of 1ml/min in isocratic mode. Quantification was achieved using an electrospray ion interface operating in positive mode, under multiple reaction monitoring (MRM) conditions. Results: The method showed excellent linearity over the concentration range of 5.00- 75.00pg/mL for sitagliptin and 0.75- 11.35pg/mL ertugliflozin. The intra-batch and inter batch precision (%CV) was ≤ 4.3% and matrix effect (%CV) was 0.02% and 0.12% for sitagliptin at HQC and LQC, respectively. Matrix effect (%CV) was 0.08% and 0.33% for ertugliflozin at HQC and LQC, respectively. Conclusion: The simplicity of the method allows for application in laboratories, presents a valuable tool for pharmacokinetic studies. The particular assay has been proficiently put on pharmacokinetic study in rats subjects.

A Novel LC-MS Method for the Determination of Abiraterone in Rat Plasma and its Application to Pharmacokinetic Studies

2021 ◽  
Vol 17 ◽  
Author(s):  
Linzhi Dai ◽  
Pei Lv ◽  
Yun He ◽  
Xiaoli Wang ◽  
Lili Chen ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Mobile Phase ◽  
High Performance ◽  
Analytical Procedure ◽  
Internal Standard ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Quadrupole Mass ◽  
Limit Of Quantitation

Background: High–performance liquid chromatography (HPLC)–ultraviolet (UV) and liquid chromatography (LC)–mass spectrometry (MS)/MS methods have been used to analyse abiraterone (ART); however, a single-quadrupole mass spectrometer with LC-MS systems has never been used to analyse ART. Objective: The study aimed to establish a novel, simple assay of quantitating ART in rat plasma through LC–MS. Method: The analytical procedure involved the extraction of ART and D4-ART (internal standard, IS) from rat plasma through simple protein precipitation. Chromatographic separation was achieved using an isocratic mobile phase (acetonitrile: 5 mM ammonium formate with 0.1% formic acid, 50:50 v/v) at a flow rate of 0.30 mL/min on a Waters XBridge® C18 column with a total run time of 5 min. LC–MS ion transitions monitored were 350.1 and 354.1 for ART and IS, respectively. The method was validated, and the results met acceptance criteria. Results: The lower limit of quantitation achieved was 1 ng/mL, and linearity was 1–8000 ng/mL. The intra- and inter-day precisions were 1.26%–14.20% and 5.49%–13.08%, respectively, in rat plasma.

Green Liquid Chromatographic Methods with Ultraviolet and Tandem Mass Spectrometry Detection: An Application to Ternary Mixture of Paracetamol, Pseudoephedrine, and Cetirizine in Capsules

2020 ◽  
Vol 103 (1) ◽  
pp. 148-155 ◽  
Author(s):  
Souha H Youssef ◽  
Dalia Mohamed ◽  
Maha A Hegazy ◽  
Amr Badawey
Keyword(s):  
Mobile Phase ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Hplc Method ◽  
Green Solvents ◽  
Chromatographic Methods ◽  
Combination Methods ◽  
Significant Difference ◽  
Acid Aqueous Solution ◽  
Liquid Chromatographic

Abstract Background: Effective chromatographic methods were developed for the determination of a multicomponent capsule prescribed for treating the common cold. Greening approaches were adopted as opposed to conventional methods. Objectives: Two novel, green chromatographic methods were established to quantitatively analyze the combination. Methods: First, an HPLC/UV method utilizing green solvents (water and ethanol) and acetic acid to adjust pH at 5 was accomplished. The stationary phase was a ZorbaxSB-C18 column (150 × 4.6 mm, 5 μm), and peaks were detected at 215 nm. The second method is a highly sensitive ultra-performance LC (UPLC)-MS/MS method in which the greening approach was established through the reduction of the analysis time (2 min), decreased solvent consumption (flow rate 300 μL/min), and the utilization of a small volume of samples (injection volume 2 μL). The mixture was separated using a UPLC-BEH C18 column (50 × 2.1 mm, 1.7 μm) with an isocratic elution using methanol–0.1% formic acid aqueous solution (60+40, v/v) as mobile phase and utilizing diphenhydramine as an internal standard. Positive-ion electrospray ionization and multiple reaction monitoring were applied for detection. Results: Recovery percentages for paracetamol, pseudoephedrine, and cetirizine were 101.70 ± 0.969, 100.18 ± 1.563, and 99.67 ± 1.429 for the HPLC method and 99.18 ± 1.172, 100.03 ± 0.883, and 99.82 ± 0.912 for the UPLC-MS/MS method, respectively. Conclusions: The proposed methods efficiently analyzed paracetamol, pseudoephedrine, and cetirizine in Allercet Cold® capsules. Validation of the proposed methods was in accordance with the International Conference on Harmonization recommendations, and statistical comparison with the reported method displayed no significant difference regarding accuracy and precision. Highlights: Paracetamol, pseudoephedrine, and cetirizine were successfully quantified using two chromatographic methods. The HPLC method developed is considered green, using water and ethanol as a mobile phase. The UPLC-MS/MS method was rapid and determined the three drugs with accuracy at nanogram levels.

Validated Microemulsion Liquid Chromatography-Fluorescence Method for the Quantification of Duloxetine and its Two Main Metabolites in Plasma: Application to Clinical Pharmacokinetic Studies

2019 ◽  
Vol 15 (4) ◽  
pp. 399-411
Author(s):  
Raniah Al-Shalabi ◽  
Mohamed Hefnawy ◽  
Haitham Alrabiah ◽  
Haya Al-Johar ◽  
Mostafa Mohammed ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Mobile Phase ◽  
Internal Standard ◽  
Direct Analysis ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Linear Calibration ◽  
Norepinephrine Reuptake Inhibitor ◽  
Development And Validation ◽  
Microemulsion Liquid Chromatography

Background: Duloxetine (DL) is a selective serotonin and norepinephrine reuptake inhibitor. The drug is used in the treatment of major depression, anxiety, pain related to diabetic peripheral neuropathy and stress urinary incontinence. </P><P> Objective: This study described, for the first time, the development and validation of a highly selective and sensitive microemulsion liquid chromatography-fluorescence (MELC-FL) method with low environmental pollution and without extraction steps for the simultaneous quantification of DL, and its two main metabolites; 5-hydroxy-6-methoxy duloxetine (5-HDL) and 4-hydroxy duloxetine glucuronide (4- HDLG) in plasma. Methods: The studied analytes and methyl paraben (an internal standard) were detected using excitation and emission wavelengths of 280 and 340 nm, respectively. The analysis was performed on Water Symmetry C18 analytical column (100 Å, 150 mm x 3.9 mm, 5 µm) by directly injecting the plasma after appropriate dilution with microemulsion mobile phase. Total analytical run time was 4 min. Results: The MELC-FL method was statistically validated according to the FDA guidelines for bioanalytical methods for linearity, accuracy, precision, specificity, robustness, and stability. Linear calibration plots were achieved in the ranges of 25-1200 ng/mL for DL and 50-1500 ng/mL for 5-HDL and 4- HDLG (r2 ≥ 0.997) in rat plasma. The intra- and inter- assay precisions and accuracy were acceptable. The overall recoveries of DL and its two main metabolites from rat plasma were between 97.12% and 103.12% with an RSD value between 0.34% and 4.57%. Conclusion: The present study supports the possible use of the microemulsion mobile phase in LC as a “greener ” mobile phase. The developed method offered an advantage in the form of direct analysis of biological samples after appropriate dilution with eco-friendly microemulsion mobile phase, which decreased the possibility of sample loss during analysis. The developed assay was successfully applied in a pharmacokinetic study and it established the applicability of the method for the determination of concentration-time profiles of DL and its two main metabolites in rat plasma after systemic administration.

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