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.

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 Effect of Citrus suavissima Hort. ex Tanaka on pharmacokinetics of erlotinib in rat plasma by UPLC-MS/MS

2020 ◽  
Author(s):  
Jinzhao Yang ◽  
Huamin Liu ◽  
Yuan Cai ◽  
Yazhen Wu ◽  
Xiaoxin Xu ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Physiological Saline ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Control Group ◽  
Sprague Dawley ◽  
Physiological Saline Solution

AbstractTwelve Sprague-Dawley rats were randomly divided into two groups: Citrus suavissima Hort. ex Tanaka group and control group (n = 6). The rats in Citrus suavissima Hort. ex Tanaka group were given Citrus suavissima Hort. ex Tanaka juices (1 mL/100 g) by oral administration each day, continued for 14 days; the rats in control group were given Stroke-physiological saline solution (1 mL/100 g) by oral administration each day, continued for 14 days. The rats of these two groups were given a single oral administration of erlotinib (20 mg/kg) on the 15th day. After blood sampling at different time points and processing, the concentrations of erlotinib in rat plasma were determined by the established ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. Chromatographic separation was achieved using a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with erlotinib-d6 as an internal standard (IS). The initial mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) with gradient elution. Multiple reaction monitoring (MRM) modes were utilized to conduct quantitative analysis. The sensitive, rapid and selective UPLC-MS/MS method was successfully applied to analyse the effect of Citrus suavissima Hort. ex Tanaka on pharmacokinetics of erlotinib in rat plasma. There were no significant differences in AUC(0−t), t1/2, Tmax, CL, Cmax between the two groups (P > 0.05). While MRT(0−t) was decreased (P < 0.05) in Citrus suavissima Hort. ex Tanaka group, compared to the control group. It showed that Citrus suavissima Hort. ex Tanaka could not affect the metabolism of erlotinib.

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

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.

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 &gt; 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.

scholarly journals A Rapid and Sensitive UPLC-MS/MS Method for Quantification of Bruceantinol in Rat Plasma and Its Application to a Pharmacokinetic Study

Planta Medica ◽  
2017 ◽  
Vol 84 (02) ◽  
pp. 111-116
Author(s):  
Jun Li ◽  
Dayong Zheng ◽  
Bixian Zhen ◽  
Yunfeng Sun ◽  
Fen Chen ◽  
...  
Keyword(s):  
Formic Acid ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Simple Liquid ◽  
Ionization Source ◽  
Brucea Javanica ◽  
Fragment Ions

AbstractBruceantinol (BOL), a quassinoid compound isolated from the fruits of Brucea javanica, has been reported to have cytotoxic and antibacterial effects. In this study, a rapid, sensitive, and specific ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed for the quantitative determination of BOL in rat plasma. The samples were treated by simple liquid-liquid extraction with ethyl acetate and separated on an UPLC BEH C18 column (2.1 mm × 50 mm) using a 3-min gradient elution scheme, which consists of water (0.1% v/v, formic acid) and methanol (0.1%, v/v, formic acid) to achieve the separation of BOL and sinomenine (IS) with high selectivity. The electrospray ionization source was used in positive ion mode; the multiple reaction monitoring quantified the target fragment ions m/z 629.6 → 569.5 for BOL and m/z 330.5 → 207.3 for IS. This work was evaluated with regards to the specificity, extraction recovery, matrix effect, linearity, accuracy, precision, stability, and dilution integrity. This approach was used to examine the pharmacokinetics of BOL in rats after oral (0.3 mg/kg) and intravenous (0.15 mg/kg) administration. BOL presented fast excretion and very low oral bioavailability.

scholarly journals Pharmacokinetics of the Couple of Radix Aconiti Lateralis Preparata and Cinnamomum Cassia in Rats with Osteoporosis with Kidney-yang Deficiency by UPLC and Microdialysis Method

2021 ◽  
Author(s):  
Yuxiao Meng ◽  
Jiaqi Guan ◽  
Liping Yao ◽  
Xiaojun Li ◽  
Luping Qin ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Cinnamic Acid ◽  
Multiple Reaction Monitoring ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Sprague Dawley ◽  
Active Ingredients ◽  
Kidney Yang Deficiency ◽  
Acquity Uplc

Abstract Background: To confirm the metabolites of the Aconite and Cinnamon herb couple in rat, and characterize its pharmacokinetics.Methods: Microdialysis probes were inserted into the jugular vein and knee joint of Sprague Dawley rat, and dialysates of different administration groups were collected. Target analytes were separated on a hydrophilic interaction liquid chromatography column (ACQUITY UPLC BEH C8 2.1×100 mm, 1.7 μm) and analyzed with an ultra-performance liquid chromatography (UPLC) under multiple reaction monitoring modes.Results: The experiment shows that the concentrations of quality of the three metabolites in mixing extraction of the herb couple were 0.3701% for trans-cinnamic acid, 0.1249 % for mesaconitine, and 0.0469 % for hypoaconitine, and Cinnamon group was 0.1731 % for trans-cinnamic acid, Aconite group were 0.0017 % for mesaconitine, and 0.0300 % for hypoaconitine. The concentrations of quality of the metabolites in rat plasma of the herb couple group were 0.0028% for trans-cinnamic acid, 0.0947% for mesaconitine, and 0.1124% for hypoaconitine. And the concentrations of quality of Aconite group and Cinnamon group were 0.0019% for trans-cinnamic acid, 0.0307% for mesaconitine, and 0.0220% for hypoaconitine. Pharmacokinetic results showed that the mean half-lives of the microdialysis samples of blood of Cinnamon group was 492.18 min for trans-cinnamic acid, and Aconite group were 102.48 min for mesaconitine and 93.27 min for hypoaconitine, and the herb couple ware 181.36 min for trans-cinnamic acid, 103.9 min for mesaconitine and 116.01 min for hypoaconitine, and the microdialysis samples of joint of Cinnamon group was 190.85 min for trans-cinnamic acid, and Aconite group were 48.51 min for mesaconitine and 46.01 min for hypoaconitine, and the herb couple was 131.19 min for trans-cinnamic acid, 49.36 min for mesaconitine and 146.68 min for hypoaconitine.Conclusions: The mixed extraction of aconite and cinnamon can promote the dissolution of the active ingredients. The herb couple can promote the absorption of the active ingredients, improve the distribution of the active ingredients in the joint and blood, prolong the half-lives of the active ingredients. It shows that the compatibility of aconite and cinnamon can increase the bioavailability of the drug and improve the clinical efficacy.

scholarly journals Effects of ovariectomy and estrogen on ischemia-reperfusion injury in hindlimbs of female rats

2001 ◽  
Vol 91 (4) ◽  
pp. 1828-1835 ◽  
Author(s):  
Nicole Stupka ◽  
Peter M. Tiidus
Keyword(s):  
Muscle Damage ◽  
Ischemia Reperfusion Injury ◽  
Serum Insulin ◽  
Ischemia Reperfusion ◽  
Neutrophil Infiltration ◽  
Female Rats ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
17Β Estradiol

The effects of estrogen and ovariectomy on indexes of muscle damage after 2 h of complete hindlimb ischemia and 2 h of reperfusion were investigated in female Sprague-Dawley rats. The rats were assigned to one of three experimental groups: ovariectomized with a 17β-estradiol pellet implant (OE), ovariectomized with a placebo pellet implant (OP), or control with intact ovaries (R). It was hypothesized that following ischemia-reperfusion (I/R), muscle damage indexes [serum creatine kinase (CK) activity, calpain-like activity, inflammatory cell infiltration, and markers of lipid peroxidation (thiobarbituric-reactive substances)] would be lower in the OE and R rats compared with the OP rats due to the protective effects of estrogen. Serum CK activity following I/R was greater ( P < 0.01) in the R rats vs. OP rats and similar in the OP and OE rats. Calpain-like activity was greatest in the R rats ( P < 0.01) and similar in the OP and OE rats. Neutrophil infiltration was assessed using the myeloperoxidase (MPO) assay and immunohistochemical staining for CD43-positive (CD43+) cells. MPO activity was lower ( P < 0.05) in the OE rats compared with any other group and similar in the OP and R rats. The number of CD43+ cells was greater ( P < 0.01) in the OP rats compared with the OE and R rats and similar in the OE and R rats. The OE rats had lower ( P < 0.05) thiobarbituric-reactive substance content following I/R compared with the R and OP rats. Indexes of muscle damage were consistently attenuated in the OE rats but not in the R rats. A 10-fold difference in serum estrogen content may mediate this. Surprisingly, serum CK activity and muscle calpain-like activity were lower ( P< 0.05) in the OP rats compared with the R rats. Increases in serum insulin-like growth factor-1 content ( P < 0.05) due to ovariectomy were hypothesized to account for this finding. Thus both ovariectomy and estrogen supplementation have differential effects on indexes of I/R muscle damage.

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

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.

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 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 ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3953 ◽  
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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