A Pharmacokinetic Study of Ephedrine and Pseudoephedrine after Oral Administration of Ojeok-San by Validated LC-MS/MS Method in Human Plasma

A sensitive and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was developed and fully validated for the simultaneous determination of ephedrine and pseudoephedrine in human plasma after oral administration of the herbal prescription Ojeok-san (OJS); 2-phenylethylamine was used as the internal standard (IS). Both compounds presented a linear calibration curve (r2 ≥ 0.99) over a concentration range of 0.2–50 ng/mL. The developed method was fully validated in terms of selectivity, lower limit of quantitation, precision, accuracy, recovery, matrix effect, and stability, according to the regulatory guidelines from the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. This validated method was successfully applied for the pharmacokinetic assessment of ephedrine and pseudoephedrine in 20 healthy Korean volunteers administered OJS.

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Liquid chromatography–tandem mass spectrometry method for determination of rivaroxaban in human plasma and its application to a pharmacokinetic study

European Journal of Mass Spectrometry ◽

10.1177/1469066719875014 ◽

2019 ◽

Vol 26 (2) ◽

pp. 91-105 ◽

Cited By ~ 2

Author(s):

Khurshid Shaikh ◽

Ashish Mungantiwar ◽

Supriya Halde ◽

Nancy Pandita

Keyword(s):

Liquid Chromatography ◽

Human Plasma ◽

Pharmacokinetic Study ◽

Internal Standard ◽

Tandem Mass ◽

Mass Spectrometric Method ◽

Limit Of Quantitation ◽

Liquid Chromatography Tandem Mass ◽

Tandem Mass Spectrometric

A high-performance liquid chromatography tandem mass spectrometric method for the determination of Rivaroxaban in human plasma has been developed and validated using Rivaroxaban D4 as an internal standard. The extraction of analyte and internal standard was accomplished by solid phase extraction technique. The method has been validated over a concentration range of 5.96–801 ng/mL. Chromatographic separations were achieved using Gemini C18, 150 mm × 4.6 mm, 5 µm, column eluted at flow rate of 1.5 mL/min with mobile phase (acetonitrile: ammonium acetate buffer (80:20 v/v)). The overall run time of method was about 1.8 min with elution times of Rivaroxaban and its internal standard Rivaroxaban D4 at around 1.18 min. The multiple reaction monitoring transitions were set at 436/145 (m/z) and 440/145 (m/z) for Rivaroxaban and Rivaroxaban D4, respectively. The calibration curves were linear (r2 ≥ 0.99) over the range of 5.96–801 ng/mL with lower limit of quantitation validated at 5.96 ng/mL. Extraction recoveries were >88% for both rivaroxaban and its stable labeled internal standard rivaroxaban D4. The inter-day/between run precisions were ranged from 1.08% to 3.75%, while accuracy ranged from 96.3% to 102%. The presented method was used in pharmacokinetic study in healthy volunteers. Results of incurred sample reanalysis were within the acceptance range of ±20% of original value, for 98.3% of samples reanalyzed. This indicated good assay precision of target analytes in their real matrix at the employed experimental conditions. The applicability of the assay for the determination of the pharmacokinetic parameters was demonstrated.

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Rapid and Sensitive Method for Quantitative Determination of Lopinavir and Ritonavir in Human Plasma by Liquid Chromatography- Tandem Mass Specrtometry

E-Journal of Chemistry ◽

10.1155/2009/709478 ◽

2009 ◽

Vol 6 (1) ◽

pp. 223-230 ◽

Cited By ~ 7

Author(s):

G. A. Temghare ◽

S. S. Shetye ◽

S. S. Joshi

Keyword(s):

Liquid Chromatography ◽

Human Plasma ◽

Solid Phase ◽

Internal Standard ◽

Therapeutic Monitoring ◽

Tandem Mass ◽

Limit Of Quantification ◽

Liquid Chromatography Tandem Mass ◽

Sensitive Method

A rapid and sensitive liquid chromatography-mass spectrometric (LC-MS-MS) method for the simultaneous determination of lopinavir and ritonavir in human plasma using abacavir as internal standard has been developed and validated. Sample preparation of plasma involved solid phase extraction. Detection was performed using an Applied Biosystems Sciex API 2000 Mass spectrometer. The assay of lopinavir and ritonavir was linear over the range of 50 ng mL-1to 20000 ng mL-1and 20 ng mL-1to 3000 ng mL-1 respectively with a precision of <15% and accuracy in the range of 85-115%. The limit of quantification in plasma for lopinavir and ritonavir was 50 ng mL-1and 20 ng mL-1respectively. The described method has the advantage of being rapid and easy and it could be applied in therapeutic monitoring of these drugs in human plasma

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Determination of Tianeptine in Tablets by High-Performance Liquid Chromatography with Fluorescence Detection

Journal of AOAC International ◽

10.1093/jaoac/90.3.720 ◽

2007 ◽

Vol 90 (3) ◽

pp. 720-724

Author(s):

Sevgi Tatar Ulu

Keyword(s):

Lower Limit ◽

High Performance ◽

Limit Of Detection ◽

Internal Standard ◽

Linear Calibration ◽

Fluorescence Detector ◽

Relative Standard ◽

Validation Parameters ◽

Limit Of Quantitation

Abstract A sensitive and selective high-performance liquid chromatographic method has been developed for the determination of tianeptine (Tia) in tablets. The method is based on derivatization of Tia with 4-chloro-7-nitrobenzofurazan (NBD-Cl). A mobile phase consisting of acetonitrile10 mM orthophosphoric acid (pH 2.5; 77 + 23) was used at a flow rate of 1 mL/min on a C18 column. The Tia-NBD derivative was monitored using a fluorescence detector, with emission set at 520 nm and excitation at 458 nm. Gabapentin was selected as an internal standard. Linear calibration graphs were obtained in the concentration range of 45300 ng/mL. The lower limit of detection (LOD) was 10 ng/mL at a signal-to-noise ratio of 4. The lower limit of quantitation (LOQ) was 45 ng/mL. The relative standard values for intra- and interday precision were <0.46 and <0.57%, respectively. The recovery of the drug samples ranged between 98.89 and 99.85%. No chromatographic interference from the tablet excipients was found. The proposed method was validated in terms of precision, robustness, recovery, LOD, and LOQ. All the validation parameters were within the acceptance range. The proposed method was applied for the determination of Tia in commercially available tablets. The results were compared with those obtained by an ultraviolet spectrophotometric method using t- and F-tests.

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Simultaneous determination of novel ketolide antibiotic nafithromycin and its major metabolite in human plasma using liquid chromatography tandem mass spectrometry

Bioanalysis ◽

10.4155/bio-2019-0153 ◽

2019 ◽

Vol 11 (19) ◽

pp. 1767-1776

Author(s):

Kiran R Patil ◽

Ravindra D Yeole ◽

Marcel de Zwart ◽

Peter Pruim

Keyword(s):

Phase I ◽

Human Plasma ◽

Internal Standard ◽

Pharmacokinetic Studies ◽

Simultaneous Quantification ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass ◽

Us Fda ◽

Standard Protein

Aim: A sensitive method to quantify nafithromycin and its N-desmethyl metabolite in human plasma was necessary for Phase I pharmacokinetic studies. Methodology: A precise and accurate LC–MS/MS bioanalytical method has been developed and validated for the simultaneous quantification of nafithromycin (NFT, WCK 4873) and N-desmethyl metabolite (M1, WCK 4978) in human plasma. Clarithromycin was used as an internal standard. Protein precipitation technique was used as sample preparation approach. The calibration curve was linear (r ≥ 0.99) over the concentration range of 10–5000 ng/ml for NFT and M1. Method was validated as per US FDA guideline. Conclusion: The proposed method was successfully applied for determination of plasma levels of the NFT and M1 during Phase I clinical studies.

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Determination of nimodipine in plasma by HPLC-MS/MS and pharmacokinetic application

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502010000400008 ◽

2010 ◽

Vol 46 (4) ◽

pp. 665-677 ◽

Cited By ~ 6

Author(s):

Demétrius Fernandes do Nascimento ◽

Manoel Odorico de Moraes ◽

Fernando Antônio Frota Bezerra ◽

Andréa Vieira Pontes ◽

Célia Regina Amaral Uchoa ◽

...

Keyword(s):

Human Plasma ◽

Internal Standard ◽

Pharmacokinetic Profile ◽

Plasma Samples ◽

Linear Calibration ◽

Limit Of Quantification ◽

Standard Curve ◽

Liquid Liquid Extraction ◽

Highly Sensitive

To develop and validate a rapid, specific and highly sensitive method to quantify nimodipine in human plasma using dibucaine as the internal standard (IS). The analyte and IS were extracted from plasma samples by liquid-liquid extraction using hexane-ethyl acetate (1:1 v/v). The chromatographic separation was performed on a Varian® Polaris C18 analytical column (3 μm, 50 x 2.0 mm) and pre-column SecurityguardTM C18 (4.0 x 3.0 mm) with a mobile phase of Acetonitrile-Ammonium acetate 0.02 ml/L (80:20v/v). The method had a chromatographic run time of 4.5 min and linear calibration curve over the range of 0.1- 40 ng/mL (r > 0.9938). The limit of quantification was 100 pg/mL. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. This validated method was successfully applied in determining the pharmacokinetic profile of nimodipine tablets of 30 mg administered to 24 healthy volunteers. The proposed method of analysis provided a sensitive and specific assay for nimodipine determination in human plasma. The time for the determination of one plasma sample was 4.5 min. This method is suitable for the analysis of nimodipine in human plasma samples collected for pharmacokinetic, bioavailability or bioequivalence studies in humans.

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Determination of Acotiamide in human plasma by LC-MS/MS and its application to a pharmacokinetic study

Current Pharmaceutical Analysis ◽

10.2174/1573412917999201110203650 ◽

2020 ◽

Vol 17 ◽

Author(s):

Qian Sun ◽

Qiao-gen Zou ◽

Yun-yan Xia ◽

Cheng-qun Han

Keyword(s):

Human Plasma ◽

Pharmacokinetic Study ◽

Ammonium Acetate ◽

Internal Standard ◽

Rat Plasma ◽

Pharmacokinetic Studies ◽

The Matrix ◽

Liquid Chromatography Tandem Mass ◽

Tandem Mass Spectrometric

Background: A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method had been developed for the quantification of acotiamide in rat plasma and been applied to pharmacokinetic studies. However, there was no LC-MS/MS method been developed for the determination of acotiamide in human plasma and its pharmacokinetic study. Objective: A simple and fast LC-MS/MS method was established and validated for the quantification of acotiamide in human Received: plasma and was applied to a pharmacokinetic study. Methods: Sample preparation was accomplished Revised: Accepted: through protein precipitation, and chromatographic separation was achieved on a Welch, Ultimate XB-C18 column (2.1×50 mm, 3 μm) with a security guard cartridge C18 using a binary gradient with DOI: mobile phase A (Methanol) and B (the solution of 10 mM Ammonium acetate with 0.1% Formic acid) at a flow rate of 400 Results: The retention time of acotiamide and its internal standard, acotiamide-d6 was 1.78 min and 1.79 min, respectively. The total run time was 4.0 min. The method was developed and validated over the concentration range of 0.500-100 ng/mL for acotiamide, with correlation coefficient greater than 0.9987. The extraction recovery was more than 108.43% and the matrix effect was not significant. The inter- and intra-day precisions were below 5.80% and accuracies ranged from 92.7 to 103.0%. Acotiamide was demonstrated to be stable in human plasma under the tested conditions. Conclusion: The validated LC-MS/MS method was successfully applied to study the pharmacokinetic profiles of acotiamide in human plasma after oral administration and has achieved satisfactory results.

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Liquid Chromatography/Tandem Mass Spectrometry for the Simultaneous Determination of Alverine and its Metabolite, Monohydroxy Alverine, in Human Plasma: Application to a Pharmacokinetic Study

E-Journal of Chemistry ◽

10.1155/2011/109414 ◽

2011 ◽

Vol 8 (1) ◽

pp. 201-211 ◽

Cited By ~ 1

Author(s):

Rahul C. Gavhane ◽

Ketan K. Nerurkar ◽

Ashok M. Kalamkar ◽

Mitesh R. Patil ◽

Satish G. Pingale ◽

...

Keyword(s):

Human Plasma ◽

Pharmacokinetic Study ◽

Solid Phase ◽

Internal Standard ◽

Selected Reaction Monitoring ◽

Limit Of Quantification ◽

Liquid Chromatography Tandem Mass ◽

Assay Precision ◽

Male Subjects

A rapid and sensitive LC-MS-MS method for the determination of alverine (ALV) and its major metabolite, monohydroxy alverine (MHA), in human plasma using imipramine as an internal standard was developed and validated. The analytes were extracted from 0.5 mL aliquots of human plasma by solid phase extraction, using oasis cartridge. Chromatographic separation was carried on Thermo Gold C18 column (50 × 4.6 mm, 5 μ) at 30 °C, with isocratic mobile phase, a flow rate of 0.4 mL/min and a total run time of 3.5 min. Detection and quantification were performed using a mass spectrometer in the selected reaction-monitoring mode with positive electrospray ionization atm/z282.3 → 91.11 for alverine,m/z298.3 → 106.9 for mono-hydroxy-alverine, andm/z281.0 → 86.0 for internal standard (IS) respectively. This assay was linear over a concentration range of 0.060-10 ng/mL with a lower limit of quantification of 0.060 ng/mL for both alverine and monohydroxy alverine. The coefficient of variation for the assay precision were <9.18% and <8.44%, the accuracy were >104.66% and >100.38% for alverine and monohydroxy alverine respectively. This method was successfully applied to a pharmacokinetic study after oral administration of alverine citrate 60 mg capsule in healthy male subjects.

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SENSITIVE BIO ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF VENETOCLAX IN HUMAN PLASMA BY LC-ESI-MS/MS

INDIAN DRUGS ◽

10.53879/id.57.06.11999 ◽

2020 ◽

Vol 57 (06) ◽

pp. 32-38

Author(s):

H. Potluri ◽

Keyword(s):

Human Plasma ◽

Method Development ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Liquid Liquid Extraction ◽

Liquid Chromatography Tandem Mass ◽

Positive Mode ◽

Method Development And Validation ◽

Development And Validation

A specific and sensitive method of liquid chromatography–tandem mass spectrometry was demonstrated for the experimental determination of venetoclax in human plasma utilising venetoclax-D8 as an internal standard. The column Xbridge C18, 50 × 4.6mm, 5 µm was used for attaining chromatographic separation by utilising 10mM ammonium formate and methanol as isocratic mobile phase in the composition ratio of 20:80 (V/V). The flow-rate selected was 0.7ml/min. Venetoclax and venetoclax-D8 are identified in multiple reaction monitoring (MRM) positive mode with proton adducts at m/z 869.53 →553.21 and m/z 877.14 → 553.23, respectively. For the successful extraction of drug as well as internal standard, liquid-liquid extraction technique was efficiently utilised. The developed technique was established in a linear concentration range of 5.0-5000.0 pg/ml along with correlation coefficient (r2) of 0.9994. Intra and inter-day precisions were found to be 0.7 to 1.90% and 0.7 to 2.0 % for venetoclax and venetoclax-D8, respectively. Accuracy was found to be within 98.6 to 101.99% and 99.17 to 101.14 % for venetoclax and venetoclax-D8, respectively. It was observed that throughout the bench top studies, post-operative stability studies and freeze-thawing cycles, venetoclax retained stability.

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A RAPID AND SENSITIVE LIQUID CHROMATOGRAPHY- MASS SPECTROMETRY/MASS SPECTROMETRY METHOD FOR ESTIMATION OF PIOGLITAZONE, KETO PIOGLITAZONE AND HYDROXY PIOGLITAZONE IN HUMAN PLASMA

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i12.20284 ◽

2017 ◽

Vol 10 (12) ◽

pp. 120

Author(s):

Revathi Naga Lakshmi Ponnuri ◽

Prahlad Pragallapati ◽

Ravindra N ◽

Venkata Basaveswara Rao Mandava

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Human Plasma ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Pharmacokinetic Parameters ◽

Validation Parameters ◽

Liquid Chromatography Tandem Mass ◽

Multiple Reaction Monitoring Mode

Objective: The main objective of the work was to develop a straightforward, fast and selective liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay for determination of pioglitazone (PG), keto pioglitazone (KPG), and hydroxy pioglitazone (HPG) in human plasma and to validate as per recent guidelines.Methods: Analyte and the internal standard (IS) were extracted from plasma through liquid-liquid extraction and chromatographed on a Xterra RP18, 100×4.6, 5 μ column using methanol: acetonitrile mixture and 10 mM Ammonium formate buffer (70:30, v/v) as the mobile phase at a flow rate of 0.7 mL/min. The API-3200 Q Trap LC-MS/MS instrument in multiple reaction monitoring mode was used for detection. Diphenhydramine was utilized as IS.Results: The linearity was established in the concentration range of 20.15-1007.58 ng/mL for PG, 20.35-1017.58 ng/mL for KPG, and 19.68-491.22 ng/mL for HPG in human plasma. All the validation parameters were well within the acceptance limits.Conclusion: A new simple LC-MS/MS method was developed for the determination of PG, KPG, and HPG in human plasma. This method can be easily applied for the estimation of pharmacokinetic parameters of PG, KPG, and HPG.

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