scholarly journals Development of a Validated UPLC-MS/MS Method for Analyzing Major Ginseng Saponins from Various Ginseng Species

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4065 ◽  
Author(s):  
Ling Yang ◽  
Chi-Lin Li ◽  
Yung-Yi Cheng ◽  
Tung-Hu Tsai
Keyword(s):  
Partition Coefficient ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Reversed Phase ◽  
Hydroxyl Groups ◽  
Ginsenoside Rb1 ◽  
Ginsenoside Re ◽  
Ginsenoside Rd

Ginsenosides, which contain one triterpene and one or more sugar moieties, are the major bioactive compounds of ginseng. The aim of this study was to develop and optimize a specific and reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the analysis of twelve different resources of ginseng. The six marker compounds of ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rc, ginsenoside Rd, ginsenoside Re, and ginsenoside Rg1, as well as an internal standard, were separated by a reversed-phase C-18 column with a gradient elution of water and methanol-acetonitrile. The multiple-reaction monitoring (MRM) mode was used to quantify and identify twelve market products. The results demonstrated that not only is the logarithm of its partition coefficient (cLog P; octanol-water partition coefficient) one of the factors, but also the number of sugars, position of sugars, and position of the hydroxyl groups are involved in the complicated separation factors for the analytes in the analytical system. If the amount of ginsenoside Rb1 was higher than 40 mg/g, then the species might be Panax quinquefolius, based on the results of the marker ginsenoside contents of various varieties. In summary, this study provides a rapid and precise analytical method for identifying the various ginsenosides from different species, geographic environments, and cultivation cultures.

scholarly journals 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

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.

Determination of JW5473 in Rat Plasma by UPLC-MS/MS and its Application to Pharmacokinetic Study of JW5473

Drug Research ◽  
2019 ◽  
Vol 69 (11) ◽  
pp. 606-611
Author(s):  
Tae Kon Kim
Keyword(s):  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Reversed Phase ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Esi Ms ◽  
Quantitation Limit ◽  
Fraction Absorbed

AbstractA sensitive method for quantitation of JW5473 in rat plasma has been established using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI/MS/MS). Tramadol was used as an internal standard. JW5473 and internal standard in plasma sample was extracted using acetonitrile (protein precipitation). A centrifuged upper layer was then evaporated and reconstituted with the mobile phase of 0.5% formic acid-acetonitrile (40:60, v/v). The reconstituted samples were injected into a C18 reversed-phase column. Using MS/MS in the multiple reaction monitoring (MRM) mode, JW5473 and tramadol were detected without severe interference from rat plasma matrix. JW5473 produced a protonated precursor ion ([M+H]+) at m/z 432.3 and a corresponding product ion at m/z 114.4. And the internal standard produced a protonated precursor ion ([M+H]+) at m/z 264.4 and a corresponding product ion at m/z 58.1. Detection of JW5473 in human plasma by the UPLC-ESI/MS/MS method was accurate and precise with a quantitation limit of 1.0 ng/mL. The validation, reproducibility, stability, and recovery of the method were evaluated. The method has been successfully applied to pharmacokinetic studies of JW5473 in rat plasma. Pharmacokinetic parameters of JW5473 was evaluated after intravenous (i. v.; at doses of 15 mg/kg) and oral (p.o.; at doses of 30 mg/kg) administration of JW5473 in rats. After p.o. administration (30 mg/kg) of JW5473, F (Fraction absorbed) value was approximately 70.5%.

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.

Simultaneous Determination of Alogliptin, Linagliptin, Saxagliptin, and Sitagliptin in Bulk Drug and Formulation by UPLC Q-TOF-MS

2020 ◽  
Vol 17 (1) ◽  
pp. 95-105
Author(s):  
Ramji Rathod ◽  
Faraat Ali ◽  
Amrish Chandra ◽  
Robin Kumar ◽  
Meenakshi Dahiya ◽  
...  
Keyword(s):  
Internal Standard ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Pharmaceutical Dosage Forms ◽  
Sensitivity And Selectivity ◽  
The Mean ◽  
Bulk Drug ◽  
Positive Ion ◽  
Higher Sensitivity

Background: A simple and sensitive Ultra Performance Liquid Chromatography-Mass Spectrometry method was developed and validated to measure the concentrations of Alogliptin (ALO), Linagliptin (LIN), Saxagliptin (SAX), and Sitagliptin (SIT) using Pioglitazone (PIO) as an internal standard. Methods: Chromatographic separation of six gliptins was achieved on a C-18 column (100×2.1 mm, 2.7 μm) using a mobile phase consisting of formic acid in water, 0.1%v/v: acetonitrile in gradient elution. Electrospray ionization (ESI) source was operated in the positive ion mode. Targeted MS/MS mode on a QTOF MS was used to quantify the drug utilizing the transitions of 340.1(m/z), 473.2 (m/z), 316.2 (m/z), 408.1 (m/z), and 357.1 (m/z) for ALO, LIN, SAX, SIT and PIO respectively. Results: As per ICH Q2R1 guidelines, a detailed validation of the method was carried out and the standard curves were found to be linear over the concentration ranges of 1516.0-4548.1 ng mL-1, 519.8- 1559.4 ng mL-1, 1531.4-4594.3 ng mL-1and 1519.6-4558.8 ng mL-1 for ALO, LIN, SAX and SIT respectively. Precision and accuracy results were within the acceptable limits. The mean recovery was found to be 98.8 _ 0.76 % (GEM), 102.2 _ 1.59 % (LIN), 95.3 _ 2.74 % (SAX) and 99.2 _ 1.75 % (SIT) respectively. Conclusions: The optimized validated UPLC QTOF-MS/MS method offered the advantage of shorter analytical times and higher sensitivity and selectivity. The optimized method is suitable for application in quantitative analysis of pharmaceutical dosage forms for QC laboratory.

scholarly journals Development and Validation of an Up-to-Date Highly Sensitive UHPLC-MS/MS Method for the Simultaneous Quantification of Current Anti-HIV Nucleoside Analogues in Human Plasma

2021 ◽  
Vol 14 (5) ◽  
pp. 460
Author(s):  
Amedeo De Nicolò ◽  
Alessandra Manca ◽  
Alice Ianniello ◽  
Alice Palermiti ◽  
Andrea Calcagno ◽  
...  
Keyword(s):  
Human Plasma ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Reversed Phase ◽  
Therapeutic Drug ◽  
People Living With Hiv ◽  
Simultaneous Quantification ◽  
Working Solution ◽  
Tenofovir Alafenamide ◽  
Combination Regimens

Therapeutic options to treat HIV infection have widened in the past years, improving both effectiveness and tolerability, but nucleoside reverse transcriptase inhibitors (NRTIs) are still considered the standard backbone of the combination regimens. Therapeutic drug monitoring (TDM) can be useful for these drugs, due to concentration–effect relationship, with risk of ineffectiveness, toxicity or adherence concerns: in this scenario, robust and multiplexed methods are needed for an effective TDM activity. In this work, the first validated ultra-high spectrometry liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method is described for the high-sensitive simultaneous quantification of all the currently used NRTIs in human plasma, including tenofovir alafenamide (TAF), following FDA and EMA guidelines. The automated sample preparation consisted in the addition of an internal standard (IS) working solution, containing stable-isotope-linked drugs, protein precipitation and drying. Dry extracts were reconstituted with water, then, these underwent reversed phase chromatographic separation: compounds were detected through electrospray ionization and multiple reaction monitoring. Accuracy, precision, recovery and IS-normalized matrix effect fulfilled guidelines’ requirements. The application of this method on samples from people living with HIV (PLWH) showed satisfactory performance, being capable of quantifying the very low concentrations of tenofovir (TFV) in patients treated with TAF.

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 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.

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.

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

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.

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