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

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.

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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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Determination of sarecycline by UPLC-MS/MS and its application to pharmacokinetic study in rats

Acta Chromatographica ◽

10.1556/1326.2020.00796 ◽

2020 ◽

Author(s):

Yonghui Shen ◽

Deru Meng ◽

Feifei Chen ◽

Hui Jiang ◽

Liming Hu ◽

...

Keyword(s):

Pharmacokinetic Study ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Gradient Elution ◽

Rat Plasma ◽

Chronic Inflammatory Disease ◽

Linear Calibration ◽

Limit Of Quantification ◽

Acquity Uplc ◽

Intravenous And Oral Administration

AbstractSarecycline is a narrow-spectrum antibiotic for the treatment of acne, which is a chronic inflammatory disease of the hair follicle sebaceous glands. In the study, UPLC-MS/MS was used to establish a rapid and accurate analytical method. The sarecycline was determined with poziotinib as internal standard (IS) in rat plasma. An ACQUITY UPLC HSS T3 column (2.1 × 100 mm, 1.8 μm) could performe chromatographic separation with the mobile phase (methanol: water of 0.1% formic acid) with gradient elution. The ions of target fragment were m/z 488.19→410.14 for sarecycline and m/z 492.06→354.55 for poziotinib, which could quantify the electrospray ionization of positive multiple reaction monitoring (MRM) mode. The linear calibration curve of the concentration range was 1–1,000 ng/mL for sarecycline with a lower limit of quantification (LLOQ) of 1 ng/mL. The mean recovery was between 82.46 and 95.85% for sarecycline and poziotinib in rat plasma. RSD for precision of inter-day and intra-day were between 3.24 and 13.36%, and the accuracy ranged from 105.26 to 109.75%. The developed and validated method was perfectly used in the pharmacokinetic study and bioavailability of sarecycline after intravenous and oral administration in rats.

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Development and Validation of a Sensitive UHPLC-MS/MS Method for the Measurement of Gardneramine in Rat Plasma and Tissues and its Application to Pharmacokinetics and Tissue Distribution Study

Molecules ◽

10.3390/molecules24213953 ◽

2019 ◽

Vol 24 (21) ◽

pp. 3953 ◽

Cited By ~ 1

Author(s):

Zhao ◽

Tan ◽

Chen ◽

Sun ◽

Wang ◽

...

Keyword(s):

Multiple Reaction Monitoring ◽

Indole Alkaloid ◽

Internal Standard ◽

Gradient Elution ◽

Rat Plasma ◽

Limit Of Quantification ◽

Tissue Samples ◽

Distribution Study

As a novel monoterpenoid indole alkaloid, gardneramine has been confirmed to possess excellent nervous depressive effects. However, there have been no reports about the measurement of gardneramine in vitro and in vivo. The motivation of this study was to establish and validate a specific, sensitive, and robust analytical method based on UHPLC-MS/MS for quantification of gardneramine in rat plasma and various tissues after intravenous administration. The analyte was extracted from plasma and tissue samples by protein precipitation with methanol using theophylline as an internal standard (I.S.). The analytes were separated on an Agilent ZORBAX Eclipse Plus C18 column using a gradient elution of acetonitrile and 0.1% formic acid in water at a flow rate of 0.3 mL/min. Gardneramine and I.S. were detected and quantified using positive electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 413.1→217.9 for gardneramine and m/z 181.2→124.1 for I.S.. Perfect linearity range was 1–2000 ng/mL with a correlation coefficient (r2) of ≥0.990. The lower limit of quantification (LLOQ) of 1.0 ng/mL was adequate for application to different preclinical studies. The method was successfully applied for determination of gardneramine in bio-samples.

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Development and Validation of UPLC-MS/MS Method for Determination of Enasidenib in Rat Plasma and Its Pharmacokinetic Application

International Journal of Analytical Chemistry ◽

10.1155/2020/5084127 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Shuang-long Li ◽

Yong-liang Zhu ◽

Yi Zhang ◽

Shu-han Liu ◽

Xiang-die Wang ◽

...

Keyword(s):

Mass Transfer ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Gradient Elution ◽

Rat Plasma ◽

Bioanalytical Method Validation ◽

Fda Approval ◽

Elution Method ◽

Acquity Uplc ◽

Development And Validation

In our research, a straightforward UPLC-MS/MS method, with diazepam as the internal standard (IS), was proposed and acknowledged to determine the concentrations of enasidenib in rat plasma. When preparing the sample, we used acetonitrile for protein precipitation. The gradient elution method was used, and the mobile phase was acetonitrile and 0.1% formic acid. Diazepam was used as the IS. We used the Acquity UPLC BEH C18 column to separate enasidenib and IS. Under the positive ion electrospray ionization (ESI) source conditions, the mass transfer pairs of enasidenib were monitored by multiple reaction monitoring (MRM) to be m/z 474.2 ⟶ 456.1 and m/z 474.2 ⟶ 267.0, and the IS mass transfer pairs were m/z 285.0 ⟶ 154.0. Enasidenib had good linearity (r2 = 0.9985) in the concentration range of 1.0–1000 ng/mL. Besides, the values of intraday and interday precision were 2.25–8.40% and 3.94–5.46%, respectively, and the range of the accuracy values varied from −1.44 to 2.34%. Matrix effect, extraction recovery, and stability were compliant with FDA approval guidelines in terms of bioanalytical method validation. We had established a new method that had been applied to the pharmacokinetic study of enasidenib in rats.

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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

International Journal of Analytical Chemistry ◽

10.1155/2019/1639619 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 1

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.

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Replacement of immunoassay by LC tandem mass spectrometry for the routine measurement of drugs of abuse in oral fluid

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1258/0004563054255632 ◽

2005 ◽

Vol 42 (4) ◽

pp. 277-284 ◽

Cited By ~ 40

Author(s):

KR Allen ◽

R Azad ◽

HP Field ◽

DK Blake

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Oral Fluid ◽

Drugs Of Abuse ◽

Multiple Reaction Monitoring ◽

Gradient Elution ◽

Tandem Mass ◽

Drug Concentrations ◽

Wide Range ◽

The Matrix

Background: There is increasing interest in the use of oral fluid as the matrix for the detection of drugs of abuse which requires the use of sensitive immunoassays to achieve the low detection limits required. The use of liquid chromatography linked to tandem mass spectrometry (LC/MS/MS) is explored as a possible replacement for immunoassay in screening for drugs of abuse in oral fluid samples. Methods: Oral fluid samples collected from 72 subjects attending an addiction clinic were screened for opiates, cocaine, methadone and benzodiazepines using both enzyme-linked immunosorbent assays (ELISA) and LC/MS/MS. The latter analysis used a short gradient elution with individual drugs detected by multiple reaction monitoring using tandem mass spectrometry. Results between the two methods were compared qualitatively using the cut-off concentrations defined by the ELISA assays. Results: With regard to the ELISA assays which show group specificity, LC/MS/ MS detected the presence of 6-monoacetylmorphine, morphine or dihydrocodeine in all but two of 49 samples positive for opiates. Of 55 samples positive for benzodiazepines by ELISA, all but two were confirmed by LC/MS/MS. Overall, LC/MS/MS compared favourably with ELISA for detection of specific drugs or their metabolites in the case of morphine, methadone and the cocaine metabolite benzoylecgonine. Many of the discrepant results between the two assays were a result of samples with drug concentrations near to the cut-off concentrations and the imprecision of these assays at very low concentrations. Conclusion: LC/MS/MS offers a more flexible, specific and sensitive alternative to the screening of oral fluid samples for drugs of abuse than ELISA. A wide range of drugs and metabolites can be detected from a single sample injection.

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Pharmacokinetics of Lusutrombopag, a Novel Thrombopoietin Receptor Agonist, in Rats by UPLC-MS/MS

International Journal of Analytical Chemistry ◽

10.1155/2020/7290470 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Bo Wang ◽

Feifei Chen ◽

Quan Zhou ◽

Yunfang Zhou ◽

Deru Meng ◽

...

Keyword(s):

Receptor Agonist ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Gradient Elution ◽

Rat Plasma ◽

Linear Calibration ◽

Limit Of Quantification ◽

Mass Spectrometric Measurement ◽

Thrombopoietin Receptor ◽

Positive Ion

Lusutrombopag is a second oral thrombopoietin (TPO) receptor agonist that selectively acts on human TPO receptors. In the study, UPLC-MS/MS was used to establish a selective and sensitive method to determine lusutrombopag with poziotinib as IS (internal standard) in rat plasma. Samples were prepared by precipitating protein with acetonitrile as a precipitant. Separation of lusutrombopag and poziotinib was performed on a CORTECS UPLC C18 column (2.1 ∗ 50 mm, 1.6 μm). The mobile phase (acetonitrile and water containing 0.1% formic acid) with gradient elution was set at a flow rate of 0.4 ml/min. The mass spectrometric measurement was conducted under positive ion mode using multiple reaction monitoring (MRM) of m/z 592.97 ⟶ 491.02 for lusutrombopag and m/z for poziotinib (IS) 492.06 ⟶ 354.55. The linear calibration curve of the concentration range was 2–2000 ng/ml for lusutrombopag, with a lower limit of quantification (LLOQ) of 2 ng/ml. RSD of interday and intraday precision were both no more than 9.66% with the accuracy ranging from 105.82% to 108.27%. The extraction recovery of lusutrombopag was between 82.15% and 90.34%. The developed and validated method was perfectly used in the pharmacokinetic study of lusutrombopag after oral administration in rats.

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

Current Pharmaceutical Analysis ◽

10.2174/1573412916666191022161501 ◽

2020 ◽

Vol 16 (4) ◽

pp. 438-445 ◽

Cited By ~ 1

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.

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Bioanalytical Assay Development and Validation for the Pharmacokinetic Study of GMC1, a Novel FKBP52 Co-chaperone Inhibitor for Castration Resistant Prostate Cancer

Pharmaceuticals ◽

10.3390/ph13110386 ◽

2020 ◽

Vol 13 (11) ◽

pp. 386

Author(s):

Oscar Ekpenyong ◽

Candace Cooper ◽

Jing Ma ◽

Naihsuan C. Guy ◽

Ashley N. Payan ◽

...

Keyword(s):

Prostate Cancer ◽

High Performance ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Gradient Elution ◽

Rat Plasma ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Elimination Half ◽

Positive Mode

Background: GMC1 (2-(1H-benzimidazol-2-ylsulfanyl)-N-[(Z)-(4-methoxyphenyl) methylideneamino] acetamide) effectively inhibits androgen receptor function by binding directly to FKBP52. This is a novel mechanism for the treatment of castration resistant prostate cancer (CRPC). Methods: an LC-MS/MS method was developed and validated to quantify GMC1 in plasma and urine from pharmacokinetics studies in rats. An ultra-high-performance liquid chromatography (UHPLC) system equipped with a Waters XTerra MS C18 column was used for chromatographic separation by gradient elution with 0.1% (v/v) formic acid in water and methanol. A Sciex 4000 QTRAP® mass spectrometer was used for analysis by multiple reaction monitoring (MRM) in positive mode; the specific ions [M+H]+m/z 340.995 → m/z 191.000 and [M+H]+ m/z 266.013 → m/z 234.000 were monitored for GMC1 and internal standard (albendazole), respectively. Results: GMC1 and albendazole had retention times of 1.68 and 1.66 min, respectively. The calibration curves for the determination of GMC1 in rat plasma and urine were linear from 1–1000 ng/mL. The LC-MS/MS method was validated with intra- and inter-day accuracy and precision within the 15% acceptance limit. The extraction recovery values of GMC1 from rat plasma and urine were greater than 95.0 ± 2.1% and 97.6 ± 4.6%, respectively, with no significant interfering matrix effect. GMC1 is stable under expected sample handling, storage, preparation and LC-MS/MS analysis conditions. Conclusions: Pharmacokinetic evaluation of GMC1 revealed that the molecule has a biexponential disposition in rats, is distributed rapidly and extensively, has a long elimination half-life, and appears to be eliminated primarily by first order kinetics.

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BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF ENTRECTINIB IN RAT PLASMA BY LIQUID CHROMATOGRAPHY–TANDEM MASS SPECTROMETRY

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2020.v13i11.39005 ◽

2020 ◽

pp. 155-163

Author(s):

PRAVALLIKA KE ◽

PRAMEELA RANI A ◽

RATNA KUMAR M

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

High Performance ◽

Method Development ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Rat Plasma ◽

Array Detector ◽

Pharmaceutical Drugs ◽

Relative Standard

Objective: The objective of the study was to develop and validate the bioanalytical liquid chromatography–mass spectrometry (LCMS/MS) method for the estimation of entrectinib in bulk and pharmaceutical drugs in rat plasma. Methods: Chromatographic separation of entrectinib with D4-entrectinib as internal standard (IS) was achieved using Waters Alliance high-performance liquid chromatography system, quaternary gradient pump of e2695, using Luna, 250×4.6 mm, 5 μm column and the mobile phase containing 0.1% formic acid and acetonitrile (ACN) within the ratio of 70:30% v/v. The flow was 1.0 ml/min; detection was carried out by absorption at 294 nm using a photodiode array detector at ambient temperature. Results: The peak of entrectinib was eluted at retention times of 5.225 min. The multiple reaction monitoring was 560.6/475.1 (m/z) for entrectinib and 580.6/496.3 (m/z) for IS entrectinib (D4). The linearity range was 1–20 ng/ml with a regression coefficient of 0.999. % relative standard deviation of peak areas of all measurements always <2.0. Conclusion: The method was successfully validated and it had been found to be within limits for accuracy, precision, and linearity and it is stable under analytical conditions used.

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