Pharmacokinetic Comparison of Isoalantolactone and Alantolactone in Rats after Administration Separately by Optimization of an UPLC-MS2Method

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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A Rapid UPLC-MS Method for Quantification of Gomisin D in Rat Plasma and Its Application to a Pharmacokinetic and Bioavailability Study

Molecules ◽

10.3390/molecules24071403 ◽

2019 ◽

Vol 24 (7) ◽

pp. 1403 ◽

Cited By ~ 2

Author(s):

Xiaoyong Zheng ◽

Feng Feng ◽

Xiunan Jiang ◽

Jieying Qiu ◽

Xiaojun Cai ◽

...

Keyword(s):

Multiple Reaction Monitoring ◽

Internal Standard ◽

Ultra Performance Liquid Chromatography ◽

Rat Plasma ◽

Ionization Source ◽

Quality Marker ◽

Liquid Chromatography Tandem Mass ◽

Bioavailability Study ◽

Multiple Reaction Monitoring Mode ◽

Positive Ion

Gomisin D, a lignan compound isolated from Fructus Schisandra, is a potential antidiabetic and anti-Alzheimer’s agent. Recently, gomisin D was used as a quality marker of some traditional Chinese medicine (TCM) formulas. In this study, a rapid ultra-performance liquid chromatography/tandem mass spectrometry method (UPLC-MS/MS) was developed and validated to quantify gomisin D in rat plasma for a pharmacokinetic and bioavailability study. Acetonitrile was used to precipitate plasma proteins. Separations were performed on a BEH C18 column with a gradient mobile phase comprising of acetonitrile and water (0.1% formic acid). An electrospray ionization source was applied and operated in the positive ion mode. The multiple reaction monitoring mode (MRM) was utilized to quantify gomisin D and nomilin (internal standard, IS) using the transitions of m/z 531.2 → 383.1 and m/z 515.3 → 161.0, respectively. The calibration curve was linear over the working range from 1 to 4000 ng/mL (R2 = 0.993). The intra- and interday precision ranged from 1.9% to 12.9%. The extraction recovery of gomisin D was in the range of 79.2–86.3%. The validated UPLC-MS/MS method was then used to obtain the pharmacokinetic characteristics of gomisin D after intravenous (5 mg/kg) and intragastric (50 mg/kg) administration to rats. The bioavailability of gomisin D was 107.6%, indicating that this compound may become a promising intragastrical medication. Our results provided useful information for further preclinical studies on gomisin D.

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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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Simultaneous LC-MS/MS Determination of Sacubitril, Valsartan and LBQ657 in Human Plasma and Its Application to Clinical Study

Journal of the Brazilian Chemical Society ◽

10.21577/0103-5053.20210068 ◽

2021 ◽

Author(s):

Yufeng Ni ◽

Yujia Zhang ◽

Chong Zou ◽

Li Ding

Keyword(s):

Human Plasma ◽

Multiple Reaction Monitoring ◽

Gradient Elution ◽

Ionization Source ◽

Internal Standards ◽

Accuracy And Precision ◽

Liquid Chromatography Tandem Mass ◽

Multiple Reaction Monitoring Mode ◽

Positive Ion

A rapid and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine sacubitril, valsartan and a metabolite of sacubitril (LBQ657) in human plasma using sacubitril-d4 and valsartan-d3 as the internal standards. Following protein precipitation, the analytes were operated on an Ultimate® XB-C18 column (2.1 × 50 mm, 3.5 μm, Welch) with a gradient elution with acetonitrile, and 5 mM ammonium acetate and 0.1% formic acid in water as the mobile phase. The detection was performed on a Triple Quad™ 4000 mass spectrometer coupled with an electrospray ionization source (ESI) under positive-ion multiple reaction monitoring mode. The linearities are 2.00-4000, 5.00-10000 and 5.00-10000 ng mL-1 for sacubitril, valsartan and LBQ657, respectively. The accuracy and precision of intra- and inter-day, dilution accuracy, recovery and stability of the method were all within the acceptable limits and no matrix effect or carryover was observed. The suitability of the method was successfully demonstrated in terms of the quantification of sacubitril, valsartan and LBQ657 in plasma samples collected from healthy Chinese volunteers in a clinical trial.

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Simultaneous Quantification of Four Ginsenosides in Rat Plasma and Its Application to a Comparative Pharmacokinetic Study in Normal and Depression Rats Using UHPLC-MS/MS

Journal of Analytical Methods in Chemistry ◽

10.1155/2021/4488822 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Lian-yun Du ◽

Tao Jiang ◽

Kun Wei ◽

Shuang Zhu ◽

Yan-long Shen ◽

...

Keyword(s):

High Performance ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Rat Plasma ◽

Comparative Pharmacokinetic ◽

Ginsenoside Rd ◽

Liquid Chromatography Tandem Mass ◽

Ginsenoside Rc ◽

Lower Limits

A sensitive method has been developed for simultaneous determination of ginsenoside Rh1 (G-Rh1), ginsenoside Rb1 (G-Rb1), ginsenoside Rc (G-Rc), and ginsenoside Rd (G-Rd) in rat plasma of normal and depression model group after oral administration of their solutions by using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-QQQ-MS). The biological samples were prepared by protein precipitation. Ginsenoside Rg3 (G-Rg3) was used as an internal standard (IS). MS analysis was performed under the multiple reaction monitoring (MRM) with electron spray ionization (ESI) operated in the negative mode. The method showed good linearity over a wide concentration range (R2 > 0.999) and obtained lower limits of quantification (LLOQ) of 5 ng/mL. The whole analysis procedure could be completed in as short as 16.5 min. The intraday precisions, interday precisions, and stabilities were less than 10%. The extraction recoveries from rat plasma were exceeded 86.0%. The results indicated that there were significant differences between the two groups on pharmacokinetics parameters; the absorptions of four analytes in the depression group were higher than those in the normal group because the liver metabolism and internal environment of the model rats had been affected.

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UPLC-MS/MS Method for the Determination of 14 Compounds in Rat Plasma and Its Application in a Pharmacokinetic Study of Orally Administered Xiaoyao Powder

Molecules ◽

10.3390/molecules23102514 ◽

2018 ◽

Vol 23 (10) ◽

pp. 2514 ◽

Cited By ~ 4

Author(s):

Mingyue Xu ◽

Zhanling Xu ◽

Qingxuan Xu ◽

Hongyue Zhang ◽

Mingyang Liu ◽

...

Keyword(s):

Pharmacokinetic Study ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Ultra Performance Liquid Chromatography ◽

Rat Plasma ◽

Chinese Herbs ◽

Tandem Mass ◽

Ionization Source ◽

Liquid Chromatography Tandem Mass ◽

Negative Ionization

Xiaoyao Powder (XYP), a common Chinese medicine, comprises eight traditional Chinese herbs and has been widely used clinically to treat liver damage and mental disorders. An ultra-performance liquid chromatography–tandem mass spectrometry method was developed to investigate the pharmacokinetics of 14 compounds (albiflorin, paeoniflorin, ferulic acid, senkyunolide I, quercetin, isoliquiritigenin, atractylenolide III, ligustilide, atractylenolide II, liquiritin, liquiritigenin, saikosaponin c, glycyrrhizic acid, and saikosaponin a) in XYP. Naringenin was used as the internal standard. The compounds were separated using an ACQUITY UPLCTM BEH C18 column (1.7 μm, 50 × 2.1 mm) with a mobile phase consisting of acetonitrile and 0.1% formic acid in water at a flow rate of 0.3 mL/min. Detection was performed on a triple-quadrupole tandem mass spectrometer using multiple reaction monitoring and an electrospray ionization source in both positive and negative ionization modes. All calibration curves exhibited good linearity (r2 > 0.9974) over the measured ranges. The intra- and inter-day precisions were within 12%, and the accuracy ranged from 89.93% to 106.64%. Extraction recovery and matrix effect results were satisfactory. The method was successfully applied in a pharmacokinetic study of the 14 compounds in rat plasma after the oral administration of XYP.

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Enantioseparation and Determination of Penconazole in Rat Plasma by Chiral LC-MS/MS: Application to a Stereoselective Toxicokinetic Study

Molecules ◽

10.3390/molecules25132964 ◽

2020 ◽

Vol 25 (13) ◽

pp. 2964

Author(s):

Siman Ma ◽

Jia Lun ◽

Yanru Liu ◽

Zhen Jiang ◽

Xingjie Guo

Keyword(s):

Multiple Reaction Monitoring ◽

Internal Standard ◽

Correlation Coefficients ◽

Rat Plasma ◽

Male Rats ◽

Ionization Source ◽

Established Method ◽

Relative Standard

In this study, a specific and sensitive method of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was developed for the determination of penconazole enantiomers in rat plasma. The enantioseparation was achieved on a Chiralpak IC column by using acetonitrile/water (80:20, v/v) as the mobile phase. Penconazole enantiomers and internal standard l-lansoprazole (IS) were detected in multiple reaction monitoring (MRM) mode with positive electrospray ionization source. The method was validated over the concentration range of 2.5–250.0 ng mL−1 for penconazole enantiomers. Good linearity was obtained for both enantiomers with correlation coefficients (R) greater than 0.995. The relative error was well within the admissible range of −1.1–3.2%, and relative standard deviation was less than 6.0%. After validation, the established method was successfully applied to a stereoselective toxicokinetic study in female and male rats after oral administration of 50 mg kg−1 racemic penconazole. This is the first experiment regarding the stereospecific toxicokinetic study of penconazole and the bioanalytical approach for its quantitation in vivo.

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

Planta Medica ◽

10.1055/s-0043-117414 ◽

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.

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Simultaneous determination of rivaroxaban and sitagliptin in rat plasma by LC–MS/MS and its application to pharmacokinetic drug-drug interaction study

Acta Chromatographica ◽

10.1556/1326.2021.00988 ◽

2021 ◽

Keyword(s):

Metabolic Pathways ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Rat Plasma ◽

Interaction Study ◽

Isocratic Elution ◽

Drug Interaction Study ◽

Positive Ion ◽

Pharmacokinetic Drug

Abstract A sensitive and accurate LC-MS/MS method was developed and validated for the simultaneous quantification of rivaroxaban (RIV) and sitagliptin (SIT) in rat plasma using apixaban as internal standard (IS). An Agilent Eclipse plus C18 column (2.1 × 100 mm, 3.5 µm, Agilent) was used for chromatographic separation with isocratic elution. Multiple reaction monitoring (MRM) using positive-ion ESI mode to monitor ion transitions of m/z 436.8→144.9 for RIV, m/z 407.7→173.8 for SIT, m/z 459.8→442.8 for IS. The procedure of method validation included selectivity, linearity, precision, accuracy, matrix effect, extraction recovery and stability were conducted according to the guidelines of EMA and FDA. The results indicated that no obvious drug-drug interactions occurred might be owing to their differences in metabolic pathways.

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Determination of Oxadixyl in Wines by Liquid Chromatography-Tandem Mass Spectrometry: Single-Laboratory and Interlaboratory Validation Study

Journal of AOAC International ◽

10.5740/jaoacint.13-359 ◽

2014 ◽

Vol 97 (6) ◽

pp. 1701-1706

Author(s):

Armen Mirzoian ◽

Jeffrey R Ammann

Keyword(s):

Validation Study ◽

High Throughput Screening ◽

Multiple Reaction Monitoring ◽

Direct Injection ◽

Ionization Source ◽

Minimal Sample ◽

The Matrix ◽

Liquid Chromatography Tandem Mass ◽

Interlaboratory Validation

Abstract A direct injection LC/MS/MS method for the determination of the pesticide oxadixyl in wines was developed and validated. A sample divert valve was used to deliver the fraction that contained oxadixyl to the mass spectrometer's electrospray ionization source. Oxadixyl was monitored and quantitated using two transitions in multiple reaction monitoring mode. The method demonstrated recoveries of 99.2 ± 2.0 and 96.7 ± 5.2% for red and white wines, respectively, a linearity range of 2–20 μg/L, LOD at 0.7 μg/L, LOQ of 2.0 μg/L, and precision values of 8.2% (RSDr) and 6.2% (RSDR). Direct injection of the wine onto a C18 ultra-performance LC column allowed automation and high throughput screening. Benefits of this approach include minimal sample preparation, short (3 min) run times, and the use of matrix-matched calibration standards, which minimize the matrix effect due to interferences from wine phenolics, sugars, and various other components. The method's performance characteristics were not statistically different for white and red wines. An additional interlaboratory validation study involved 12 laboratories and demonstrated good data agreement with HorRat values ranging from 0.23 to 0.52.

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Liquid Chromatography Tandem Mass Spectrometric Analytical Method for Study of Colchicine in Rats Given Low Doses

Processes ◽

10.3390/pr9112007 ◽

2021 ◽

Vol 9 (11) ◽

pp. 2007

Author(s):

Hamdah M. Al Nebaihi ◽

Tyson S. Le ◽

Neal M. Davies ◽

Dion R. Brocks

Keyword(s):

Whole Blood ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Rat Plasma ◽

Low Doses ◽

Blood Concentrations ◽

Liquid Chromatography Tandem Mass ◽

Sensitivity And Selectivity ◽

Tandem Mass Spectrometric ◽

Lower Limits

A selective and sensitive assay was developed for colchicine in rat specimens. Colchicine and its deuterated analog (as internal standard, IS) were extracted from rat specimens (minimal 0.1 mL plasma, whole blood, or urine) using liquid-liquid extraction with n-hexane:dichloromethane:isopropanol. The mobile phase (formic acid: ammonium acetate: methanol) was pumped with uniform flow through an octadecylsilane analytical column. Detection was carried out by electrospray positive ionization in the multiple-reaction monitoring mode. The assay (total run time <3 min) had excellent linearity over a wide (400–800-fold) concentration range. The mean absolute recovery was >96.8%. The intra- and inter-day coefficients of variation were ˂15%, with lower limits of quantitation of 0.5 ng/mL in 0.1 mL of rat plasma. The method also provided the same lower limits of quantitation in urine and whole blood with 0.1 mL volumes, and 0.1 ng/mL using 0.5 mL of rat plasma. The blood-to-plasma ratio was >1. Rats had measurable colchicine blood concentrations for at least 24 h after intravenous doses of 0.1 mg/kg. The method possessed suitable measures of sensitivity and selectivity for detecting colchicine in several specimen types in rats given low doses.

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