Determination of eugenitin in mouse blood by ultra-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study

Abstract Eugenitin is a non-volatile chromone derivative which is always found in dried flower buds of Syzygium aromaticum L. (Merr.) & L.M. Perry. Until now, there were no reports about the pharmacokinetics of eugenitin in biological fluids. A UPLC-MS/MS method developed to determine eugenitin in mouse blood. The blood samples were prepared by protein precipitation with acetonitrile. Chrysin (internal standard, IS) and eugenitin were gradient eluted by mobile phase of acetonitrile and water (0.1% formic acid) in a BEH C18 column. The multiple reaction monitoring (MRM) of m/z 221.1→206.0 for eugenitin and m/z 255.1→152.9 for IS with an electrospray ionization (ESI) source was used for quantitative detection. The calibration curve ranged from 0.5 to 500 ng/mL (r > 0.995). The accuracy ranged from 98 to 113%, the precision was less than 12%, and the matrix effect was between 86 and 94%, the recovery was better than 81%. The developed method was successfully used for pharmacokinetics of eugenitin in mice after intravenous (5 mg/kg) and oral (20 mg/kg) administration, and the absolute availability of eugenitin was 12%.

Download Full-text

Development of a rapid UPLC-MS/MS method for the determination of toddalolactone in mouse blood and its application in pharmacokinetics

Acta Chromatographica ◽

10.1556/1326.2020.00864 ◽

2021 ◽

Author(s):

Jing Zhou ◽

Hongzhe Wang ◽

Caiyun Miao ◽

Yunxi Yao ◽

Jianshe Ma

Keyword(s):

Matrix Effects ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Absolute Bioavailability ◽

Quantitative Detection ◽

Ionization Source ◽

Mouse Blood ◽

The Matrix ◽

Product Ions

AbstractA rapid and simple UPLC-MS/MS method was developed to determine toddalolactone in mouse blood and applied to measure the pharmacokinetics of toddalolactone in mice. Blood samples were first preprocessed by ethyl acetate liquid-liquid extraction. Oxypeucedanin hydrate (internal standard, IS) and toddalolactone were gradient eluted from a UPLC BEH C18 column using a mobile phase consisting of acetonitrile and water (0.1% formic acid). Using electrospray ionization (ESI) as the ionization source, multiple reaction monitoring was used to detect the precursor and product ions of m/z 309.2 and 205.2, respectively, for toddalolactone and of m/z 305.1 and 203.0 for IS, respectively, for quantitative detection. A calibration curve was run over the concentration range of 5–4,000 ng/mL (r > 0.995). The matrix effects ranged from 93.5 to 98.4%, and the recovery was higher than 77.3%. The precision was less than 13%, and the accuracy ranged from 90.9 to 108.4%. The developed UPLC-MS/MS method was successfully used for measuring the pharmacokinetics of toddalolactone in mice after oral (20 mg/kg) and intravenous administration (5 mg/kg), and the absolute bioavailability of toddalolactone was 22.4%.

Download Full-text

Simultaneous Determination of Six Uncaria Alkaloids in Mouse Blood by UPLC–MS/MS and Its Application in Pharmacokinetics and Bioavailability

BioMed Research International ◽

10.1155/2020/1030269 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Lianguo Chen ◽

Jianshe Ma ◽

Xianqin Wang ◽

Meiling Zhang

Keyword(s):

Simultaneous Determination ◽

Oral Absorption ◽

Matrix Effects ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Gradient Elution ◽

Mouse Blood ◽

The Matrix ◽

Liquid Chromatography Tandem Mass

A specific ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the simultaneous determination of six Uncaria alkaloids in mouse blood with midazolam as the internal standard (IS). Only 20 μL blood was needed for sample preparation, and the protein was precipitated with acetonitrile. The UPLC BEH C18 column (2.1 mm×100 mm, 1.7 μm) was used for chromatographic separation. The mobile phase consisted of 0.1% formic acid and acetonitrile with gradient elution within 5.5 min. Multiple reaction monitoring (MRM) and the positive electrospray ionization model were used for quantitative analysis. The accuracy of the UPLC-MS/MS method ranged from 86.5% to 110.4%. The precision for intraday and interday was ≤15% each. The mean recovery and the matrix effects were found to be 64.4-86.8% and 94.1-109.4%, respectively. The calibration curves in blood were linear in the range of 1-1000 ng/mL with a favorable correlation coefficient (r2) of 0.995. The pharmacokinetic results showed that six Uncaria alkaloids metabolized rapidly in mice with a half-life between 0.6 h and 4.4 h. The bioavailability of corynoxeine, isocorynoxeine, rhynchophylline, isorhynchophylline, hirsutine, and hirsuteine was 27.3%, 32.7%, 49.4%, 29.5%, 68.9%, and 51.0%, respectively, which showed satisfactory oral absorption of each alkaloid.

Download Full-text

Pharmacokinetics of ebeiedinone in mouse blood by UPLC–MS/MS

Acta Chromatographica ◽

10.1556/1326.2019.00680 ◽

2020 ◽

Vol 32 (3) ◽

pp. 194-198

Author(s):

Yongxi Jin ◽

Yuyan Chen ◽

Jiawen Liu ◽

Xi Bao ◽

Yinghao Zhi ◽

...

Keyword(s):

Pharmacokinetic Study ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Ultra Performance Liquid Chromatography ◽

Absolute Bioavailability ◽

Mouse Blood ◽

Limit Of Quantification ◽

Chromatography Tandem Mass Spectrometry ◽

The Matrix ◽

Liquid Chromatography Tandem Mass

An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was established to determine ebeiedinone in mouse blood, and the pharmacokinetics of ebeiedinone after intravenous (0.5 mg/kg) and oral (2, 4, and 8 mg/kg) administration was studied. Twenty-four mice were randomly divided into 4 groups, 1 group was for intravenous administration (0.5 mg/kg), and other 3 groups were for oral administration (2, 4, and 8 mg/kg), with 6 rats in each group. Yubeinine was used as an internal standard. Multiple reaction monitoring (MRM) mode was used to quantitatively analyzed ebeiedinone m/z 414.4 → 91.1 and the internal standard m/z 430.4 → 412.3 in the electrospray ionization (ESI) positive interface. In the concentration range of 1–2000 ng/mL, the ebeiedinone in the mouse blood was linear (r2 > 0.995), and the lower limit of quantification was 1.0 ng/mL. In the mouse blood, the intra-day precision coefficient of variation (CV) was less than 15%, and the inter-day precision CV was less than 15%. The accuracy ranged from 85.4% to 114.6%, and the average recovery was higher than 61.3%. The matrix effect was between 87.0% and 106.5%. These data met the pharmacokinetic study requirements of ebeiedinone. The UPLC–MS/MS method was sensitive, rapid, and selective and was successfully applied to the pharmacokinetic study of ebeiedinone in mice. The absolute bioavailability of ebeiedinone was 30.6%.

Download Full-text

A Novel UPLC-MS/MS Assay for the Measurement of Linezolid and its Metabolite PNU-142300 in Human Serum and its Application to Patients With Renal Insufficiency

Frontiers in Pharmacology ◽

10.3389/fphar.2021.641872 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yingying Wang ◽

Er-min Gu ◽

Xiaoxiang Du ◽

Ren-ai Xu ◽

Guanyang Lin

Keyword(s):

Liquid Chromatography ◽

Renal Insufficiency ◽

Human Serum ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Gradient Elution ◽

Ultra Performance Liquid Chromatography ◽

Serum Samples ◽

The Matrix ◽

Liquid Chromatography Tandem Mass

The contribution of the metabolites of linezolid to the associated myelosuppression is unknown in patients who are renal impairment. In this research, the purpose of our experiment was to explore and develop a quick and robust ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for the determination of linezolid and its metabolite PNU-142300 in human serum simultaneously. The analytes were prepared using a simple and convenient approach with acetonitrile for protein crash, and then separated from the matrix on a Waters Acquity Ultra performance liquid chromatography (UPLC) BEH C18 (2.1 mm × 50 mm, 1.7 μm) column in a program of gradient elution, where the mobile phase was consisted of water with 0.1% formic acid and acetonitrile, and was placed at 0.40 ml/min flow rate. Multiple reaction monitoring (MRM) was employed and conducted for UPLC-MS/MS detection with ion transitions at m/z 338.01 → 296.03 for linezolid, m/z 369.96 → 327.98 for PNU-142300 and m/z 370.98 → 342.99 for tedizolid (Internal standard, IS), respectively. This method had good linearity respectively in the calibration range of 0.01–20 μg/ml for linezolid, and 0.05–100 μg/ml for PNU-142300. In the intra- and inter-day, the precision of linezolid and PNU-142300 was below 14.2%, and the accuracy in this method was determined to be from −9.7 to 12.8%. In addition, recovery and matrix effect of the analytes were all found to be acceptable, and the analytes during the assay and storage in serum samples were observed to be stable. The novel optimized UPLC-MS/MS assay was also successfully employed to determine the concentration levels of linezolid and PNU-142300 in human serum. The results showed that linezolid-associated myelosuppression occurs more frequently in patients with renal insufficiency, and the metabolite-to-parent concentration ratio of PNU-142300 is predicted to reduce this toxicity of myelosuppression.

Download Full-text

Pharmacokinetics and bioavailability of liensinine in mouse blood by UPLC-MS/MS

Acta Chromatographica ◽

10.1556/1326.2020.00847 ◽

2020 ◽

Author(s):

Shuhua Tong ◽

Yuqi Zeng ◽

Jianshe Ma ◽

Congcong Wen

Keyword(s):

Pharmacokinetic Study ◽

Mobile Phase ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Quantitative Detection ◽

Reaction Monitoring ◽

Mouse Blood ◽

Blood Samples ◽

The Matrix ◽

Better Than

AbstractLiensinine is a bisbenzyltetrahydroisoquinoline alkaloid extracted from lotus (Nelumbo nucifera GAERTNER., Nelumbonaceae), especially in its embryo loti “Lien Tze Hsin” (green embryo of mature seed). A rapid and simple UPLC-MS/MS method was developed to determine liensinine in mouse blood and its application to a pharmacokinetic study. The blood samples were preprocessed by protein precipitation using acetonitrile. Midazolam (internal standard, IS) and liensinine were gradient eluted by mobile phase of methanol and water (0.1% formic acid) in a Waters UPLC BEH C18 column. The multiple reaction monitoring of m/z 611.3 → 206.1 for liensinine and m/z 326.2 → 291.1 for IS with an electrospray ionization (ESI) source was used for quantitative detection. The calibration curve ranged from 0.5 to 400 ng/mL (r > 0.995). The accuracy ranged from 92.2 to 108.2%, the precision of intra-day and inter-day was less than 14%, and the matrix effect was between 100.0% and 109.6%, the recovery was better than 71.0%. The developed UPLC-MS/MS method was successfully used for a pharmacokinetic study of liensinine in mice after oral (5 mg/kg) and intravenous administration (1 mg/kg), and the absolute availability of liensinine was 1.8%.

Download Full-text

Pharmacokinetic Study of Deltaline in Mouse Blood Based on UPLCMS/ MS

Current Pharmaceutical Analysis ◽

10.2174/1573412914666181011124515 ◽

2019 ◽

Vol 15 (2) ◽

pp. 194-199 ◽

Cited By ~ 4

Author(s):

Huanchun Song ◽

Yiwei Huang ◽

Dongqing Zhu ◽

Shuhua Tong ◽

Meiling Zhang ◽

...

Keyword(s):

Intravenous Administration ◽

Pharmacokinetic Study ◽

Internal Standard ◽

Gradient Elution ◽

Ultra Performance Liquid Chromatography ◽

Mouse Blood ◽

Limit Of Quantitation ◽

The Matrix ◽

Liquid Chromatography Tandem Mass ◽

Precipitate Protein

Introduction: Deltaline, an aconitine-type alkaloid, was detected in mouse blood using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method, and the pharmacokinetics of deltaline following intravenous administration in mice was studied. </P><P> Materials and Methods: The gelsenicine was used as the internal standard (IS). Deltaline and IS were eluted at a flow rate of 0.4 ml/min and separated on a UPLC BEH C18 column by gradient elution using acetonitrile and 10 mmol/L ammonium acetate (0.1% formic acid) as a mobile phase. The following transitions were obtained at m/z 508.2→75.0 for deltaline and m/z 327.1→107.8 for gelsenicine in multiple reactions monitoring mode. Acetonitrile was used to precipitate protein. Six mice after intravenous administration of a single dose of deltaline (1 mg/kg), 20-µL blood samples from each mouse were collected from the tail vein. Results: The UPLC-MS/MS method was sensitive and linear (r>0.995) with a lower limit of quantitation (LLOQ) of 0.1 ng/mL over the range of 0.1-500 ng/mL. Intra- and inter-day precisions were below 13%, the accuracy range was between 88.0% and 108.2%, the recovery was higher than 90.1%, and the matrix effect was between 102.9% and 108.1%. Conclusion: The method was sensitive, fast, specific, and has been successfully applied to a pharmacokinetic study of deltaline after intravenous administration.

Download Full-text

Determination of narciclasine in mouse blood by UPLC-MS/MS and its application to a pharmacokinetic study

Acta Chromatographica ◽

10.1556/1326.2021.00865 ◽

2021 ◽

Author(s):

Ke Ren ◽

Tiantian Feng ◽

Hai Shi ◽

Jianshe Ma ◽

Yongxi Jin

Keyword(s):

Intravenous Administration ◽

Pharmacokinetic Study ◽

Mobile Phase ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Hydroxy Derivative ◽

Reaction Monitoring ◽

Mouse Blood ◽

The Matrix

AbstractNarciclasine is a 7-hydroxy derivative of lycorisidine. It was the first alkaloid isolated from the stem of narcissus (Amaryllidaceae) in 1967. Six mice were given narciclasine (5 mg/kg) by intravenous administration. A UPLC-MS/MS method was developed to determine narciclasine in mouse blood. Tectorigenin (internal standard, IS) and narciclasine were gradient eluted by mobile phase of methanol and 0.1% formic acid in a BEH C18 column. The multiple reaction monitoring (MRM) of m/z 308.1→248.1 for narciclasine and m/z 301.1→286.0 for IS with an electrospray ionization (ESI) source was used for quantitative determination. The calibration curve ranged from 1 to 6,000 ng/mL. The accuracy was from 92.5 to 107.3%, and the matrix effect was between 103.6 and 107.4%. The developed UPLC-MS/MS method was successfully applicated to a pharmacokinetic study of narciclasine in mice after intravenous administration (5 mg/kg).

Download Full-text

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.

Download Full-text

P63 UPLC/MS/MS assay for the simultaneous determination of seven antibiotics in human serum – application to pediatric studies

Archives of Disease in Childhood ◽

10.1136/archdischild-2019-esdppp.101 ◽

2019 ◽

Vol 104 (6) ◽

pp. e43.2-e43

Author(s):

S Magreault ◽

O Chaussenery-Lorentz ◽

T Storme ◽

E Jacqz-Aigrain

Keyword(s):

Multiple Reaction Monitoring ◽

Internal Standard ◽

Ultra Performance Liquid Chromatography ◽

Routine Activity ◽

Therapeutic Drug ◽

Pharmacokinetic Studies ◽

Pediatric Dose ◽

Liquid Chromatography Tandem Mass ◽

Sampling Volume ◽

Acquity Uplc

BackgroundAntimicrobials are widely used in children but pediatric dose regimens are not always validated, and PK studies, required to validate dosage, are difficult to conduct in children. Low sampling volume limits the number of PK samples drawn per patient and analytical methods adapted to small volumes are not always available. Due to the wide inter-patient pharmacokinetic (PK) variability in children, particularly neonates, therapeutic drug monitoring is required to adapt dosage to individual patients. In such clinical and analytical context, our aim was to develop a unique, rapid and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay to quantify 7 antibiotics (amoxicillin, azithromycin, cefotaxime, ciprofloxacin, meropenem, metronidazole and piperacillin) in low sample volumes (50 µL) for both routine monitoring and pharmacokinetic studies.MethodsAfter protein precipitation by acetonitrile, the antibiotics and their associated deuterated internal standard were separated on a Waters Acquity UPLC HSS T3 (100 mm x 2.1 mm; 1.8 µm). The mobile phases consisted of a gradient of ammonium acetate (pH 2.4; 5mM) and acetonitrile acidified with 0.1% (v/v) formic acid (started ratio of 93:7, v/v), run at 0.5 mL/min flow rate (total run time: 2.75 min). Ions were detected in the turbo-ion-spray-positive and multiple-reaction-monitoring modes.ResultsThis method was linear from 0.1–50 µg/mL. Accuracy and precision were evaluated using Quality Control (2, 10, 35 µg/mL). Validation of the method proved that precision, selectivity and stability were all within the recommended limits.ConclusionThis method has the advantage of a unique, efficient and standardized analytical tool for rapid measurement of 7 antibiotics in low blood volume. It has been successfully applied for routine activity and pharmacokinetic studies in children and neonates.Disclosure(s)Nothing to disclose.

Download Full-text

Determination of bosutinib in mice plasma and tissue by UPLC-MS/MS and its application to the pharmacokinetic and tissue distribution study

Analytical Methods ◽

10.1039/c5ay01529d ◽

2015 ◽

Vol 7 (21) ◽

pp. 9184-9189 ◽

Cited By ~ 2

Author(s):

Linxia Wang ◽

Luming Tang ◽

Yi Zheng ◽

Guoquan Pan ◽

Wei Zhu ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Internal Standard ◽

Ultra Performance Liquid Chromatography ◽

Tandem Mass ◽

Distribution Study ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass ◽

Tissue Distribution Study

A sensitive and rapid ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine bosutinib in mice plasma and tissue using diazepam as the internal standard (IS).

Download Full-text