Pharmacokinetics of ligustroflavone in rats and tissue distribution in mice by UPLC–MS/MS

An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for quantification of ligustroflavone, which was then applied in pharmacokinetics study in rat and tissue distribution in mouse. Twelve male Sprague Dawley rats were used for pharmacokinetics after intravenous (2 or 8 mg/kg) administration of ligustroflavone, six rats for each dose. Twenty-five mice were randomly divided into 5 groups (5 mice for each group, 1 group for each time point) and received 16 mg/kg ligustroflavone via intraperitoneal administration. The linear range of the calibration curve was over 2–2000 ng/mL for ligustroflavone in rat plasma and mouse tissues. The intra-day and inter-day precision expressed in % RSD were less than 14%, and the accuracy was between 88.5% and 108.4%. The tissue distribution results indicated that ligustroflavone diffuses rapidly and widely into major organs. The level of ligustroflavone was highest in the mouse liver, followed by the kidney, spleen, and lung. The overwhelming accumulation in the liver indicated that the liver was responsible for the extensive metabolism.

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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 Blood (100 μL) was withdrawn from the caudal vein at 5 and 30 min and 1, 2, 4, 6, 8, 12, and 24 h after administration.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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Pharmacokinetic Comparison of Isoalantolactone and Alantolactone in Rats after Administration Separately by Optimization of an UPLC-MS2Method

Journal of Chemistry ◽

10.1155/2014/354618 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Renjie Xu ◽

Mengyue Wang ◽

Ying Peng ◽

Xiaobo Li

Keyword(s):

Multiple Reaction Monitoring ◽

Internal Standard ◽

Rat Plasma ◽

Sprague Dawley ◽

Ionization Source ◽

Fragment Ions ◽

Sprague Dawley Rats ◽

Liquid Chromatography Tandem Mass ◽

Positive Ion

Isoalantolactone and alantolactone are two major active ingredients that are present in many medicinal plants. In this study, a sensitive and rapid ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for determination of the two compounds in rat plasma, separately. In this method, an electrospray ionization source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) was selected for quantification using target fragment ions 233.2→187.1 for isoalantolactone (alantolactone) and 245.1→189.1 for internal standard (IS). Retention time of the lactones and IS was within 3.0 min. Further calibration suggested a linear regression can be calculated within 2.5–500 ng/mL for isoalantolactone and 4–500 ng/mL for alantolactone. This method was used to compare the pharmacokinetic characteristics of isoalantolactone and alantolactone at a single dose of 5 mg/kg into male Sprague-Dawley rats by intravenous administration separately. The levels oft1/2, Kel, CL,Cmax, and AUC were significantly increased in the alantolactone group compared to isoalantolactone. These results suggested that isoalantolactone was distributed and eliminated more rapidly than alantolactone in rats when administered, respectively.

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Pharmacokinetics and pharmacodynamics of cyclopropylfentanyl in male rats

Psychopharmacology ◽

10.1007/s00213-021-05981-x ◽

2021 ◽

Author(s):

Marianne Skov-Skov Bergh ◽

Inger Lise Bogen ◽

Nancy Garibay ◽

Michael H. Baumann

Keyword(s):

High Performance ◽

Parent Drug ◽

Rat Plasma ◽

Male Rats ◽

Sprague Dawley ◽

Limit Of Quantification ◽

Sprague Dawley Rats ◽

Liquid Chromatography Tandem Mass ◽

Blood Specimens

Abstract Background Illicitly manufactured fentanyl and its analogs are a major driving force behind the ongoing opioid crisis. Cyclopropylfentanyl is a fentanyl analog associated with many overdose deaths, but limited knowledge is available about its pharmacology. In the present study, we developed a bioanalytical method for the determination of cyclopropylfentanyl and its main metabolite cyclopropylnorfentanyl and evaluated pharmacokinetic-pharmacodynamic relationships in rats. Method An ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for determination of cyclopropylfentanyl and cyclopropylnorfentanyl in rat plasma. Male Sprague–Dawley rats fitted with jugular catheters and temperature transponders received cyclopropylfentanyl (30, 100, and 300 μg/kg) or saline subcutaneously. Blood specimens were withdrawn over an 8-h time period, along with measurements of pharmacodynamic endpoints. Results The analytical method was validated, and both analytes exhibited a low limit of quantification (15 pg/mL). Cyclopropylfentanyl caused dose-related increases in hot plate latency (ED50 = 48 µg/kg) and catalepsy (ED50 = 87 µg/kg) and produced long-lasting hypothermia at the highest dose. Plasma cyclopropylfentanyl rose rapidly in a dose-related fashion, reaching maximal concentration (Cmax) after 15–28 min, whereas metabolite Cmax occurred later at 45–90 min. Cyclopropylfentanyl Cmax values were similar to concentrations measured in non-fatal intoxications in humans; however, differences in parent drug: metabolite ratio indicated possible interspecies variance in metabolism. Conclusion Our study shows that cyclopropylfentanyl produces typical opioid-like effects in male rats. Cyclopropylfentanyl displays much greater analgesic potency when compared to morphine, suggesting that cyclopropylfentanyl poses increased overdose risk for unsuspecting users.

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Effect of the Phragmitis Rhizoma Aqueous Extract on the Pharmacokinetics of Docetaxel in Rats

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190419110724 ◽

2019 ◽

Vol 22 (5) ◽

pp. 326-332

Author(s):

Sarah Shin ◽

No Soo Kim ◽

Young Ah Kim ◽

Hea Ry Oh ◽

Ok-Sun Bang

Keyword(s):

Aqueous Extract ◽

Statistical Significance ◽

Ultra Performance Liquid Chromatography ◽

Pharmacokinetic Parameters ◽

Control Group ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Liquid Chromatography Tandem Mass ◽

Mass Spectrometry System ◽

Phragmitis Rhizoma

Background: Traditionally, Phragmitis rhizoma has been prescribed to relive a fever, vomiting, dysuria, and constipation, and to promote secretion of fluids. In addition, recent studies have reported its efficacy as a diuretic and antiemetic. Our previous study demonstrated that the Phragmitis rhizoma aqueous extract (EPR) ameliorates docetaxel (DTX)-induced myelotoxicity. Aim and Objective: This study was aimed to investigate the effects of EPR on the pharmacokinetics of DTX in Sprague–Dawley rats. Materials & Methods: The animals received an intravenous injection of DTX (5 mg/kg) with or without oral EPR (100 mg/kg) pretreatment for 1 or 6 days. The pharmacokinetics of plasma DTX was analyzed using an ultra-performance liquid chromatography-tandem mass spectrometry system, and pharmacokinetic parameters were estimated via noncompartmental analysis. Results: Relative to the control group (DTX alone), EPR pretreatment did not affect significantly the overall profiles of plasma DTX levels. Consecutively pretreated EPR for 6 days slightly altered AUC0-t and Cmax of DTX by 122 and 145.9%, respectively, but these data did not reach the threshold of statistical significance (p > 0.05). Conclusion: These results indicate that DTX exposure may not be affected by EPR treatment at the dose level used in this study, suggesting that oral EPR can be used safely when taken with intravenously injected DTX. However, further studies under the stringent conditions are needed when chronic treatment of EPR and anticancer drug.

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Pharmacokinetic Interaction Study of Ketamine and Rhynchophylline in Rat Plasma by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry

BioMed Research International ◽

10.1155/2018/6562309 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Lianguo Chen ◽

Weiwei You ◽

Dingwen Chen ◽

Yuan Cai ◽

Xianqin Wang ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Intraperitoneal Administration ◽

Pharmacokinetic Interaction ◽

Ultra Performance Liquid Chromatography ◽

Rat Plasma ◽

Tandem Mass ◽

Interaction Study ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass

Eighteen Sprague-Dawley rats were randomly divided into three groups: ketamine group, rhynchophylline group, and ketamine combined with rhynchophylline group (n= 6). The rats of two groups received a single intraperitoneal administration of 30 mg/kg ketamine and 30 mg/kg rhynchophylline, respectively, and the third group received combined intraperitoneal administration of 30 mg/kg ketamine and 30 mg/kg rhynchophylline together. After blood sampling at different time points and processing, the concentrations of ketamine and rhynchophylline 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, 1.7μm) with carbamazepine 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 ofm/z238.1 → 179.1 for ketamine,m/z385.3 → 159.8 for rhynchophylline, andm/z237.3 → 194.3 for carbamazepine (IS) were utilized to conduct quantitative analysis. Calibration curve of ketamine and rhynchophylline in rat plasma demonstrated good linearity in the range of 1-1000 ng/mL (r > 0.995), and the lower limit of quantification (LLOQ) was 1 ng/mL. Moreover, the intra- and interday precision relative standard deviation (RSD) of ketamine and rhynchophylline were less than 11% and 14%, respectively. This sensitive, rapid, and selective UPLC-MS/MS method was successfully applied to pharmacokinetic interaction study of ketamine and rhynchophylline after intraperitoneal administration. The results showed that there may be a reciprocal inhibition between ketamine and rhynchophylline.

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Tissue Accumulations of Toxic Aconitum Alkaloids after Short-Term and Long-Term Oral Administrations of Clinically Used Radix Aconiti Lateralis Preparations in Rats

Toxins ◽

10.3390/toxins11060353 ◽

2019 ◽

Vol 11 (6) ◽

pp. 353 ◽

Cited By ~ 2

Author(s):

Xiaoyu Ji ◽

Mengbi Yang ◽

Ka Hang Or ◽

Wan Sze Yim ◽

Zhong Zuo

Keyword(s):

Ultra Performance Liquid Chromatography ◽

Therapeutic Effects ◽

Sprague Dawley ◽

Short Term ◽

Sprague Dawley Rats ◽

Liquid Chromatography Tandem Mass ◽

Relevant Dose ◽

Radix Aconiti ◽

Toxic Alkaloids

Although Radix Aconiti Lateralis (Fuzi) is an extensively used traditional Chinese medicine with promising therapeutic effects and relatively well-reported toxicities, the related toxic aconitum alkaloid concentrations in major organs after its short-term and long-term intake during clinical practice are still not known. To give a comprehensive understanding of Fuzi-induced toxicities, current study is proposed aiming to investigate the biodistribution of the six toxic alkaloids in Fuzi, namely Aconitine (AC), Hypaconitine (HA), Mesaconitine (MA), Benzoylaconine (BAC), Benzoylhypaconine (BHA) and Benzoylmesaconine (BMA), after its oral administrations at clinically relevant dosing regimen. A ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for simultaneous quantification of six toxic alkaloids in plasma, urine and major organs of Sprague Dawley rats after oral administrations of two commonly used Fuzi preparations, namely Heishunpian and Paofupian, at their clinically relevant dose for single and 15-days. Among the studied toxic alkaloids and organs, BMA demonstrated the highest concentrations in all studied organs with liver containing the highest amount of the studied alkaloids, indicating their potential hepatotoxicity. Moreover, tissue accumulation of toxic alkaloids after multiple dose was observed, suggesting the needs for dose adjustment and more attention to the toxicities induced by chronic use of Fuzi in patients.

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