scholarly journals Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4232
Author(s):  
Shereen Mowaka ◽  
Nermeen Ashoush ◽  
Mariam Tadros ◽  
Noha El Zahar ◽  
Bassam Ayoub
Keyword(s):  
Human Plasma ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Average Concentration ◽  
Pharmacokinetic Parameters ◽  
Limit Of Quantification ◽  
Healthy Human ◽  
Tertiary Butyl ◽  
Human Volunteers ◽  
The Matrix

Enhancing drug extraction from human plasma is a challenging approach that critically affects pharmacokinetic and any further clinical studies based on the drug Cmin and Cmax values. It also has a serious impact on the sensitivity and the lower limit of quantification (LLOQ) value of the bio-analytical methods. An advanced liquid chromatography tandem mass spectrometry (LC-MS/MS) bio-analytical method of omarigliptin (25–1000 nM) was established in human plasma using one-step liquid-liquid extraction. Alogliptin was used as an internal standard (IS) to attain good recovery and reproducibility while reducing the effects of the matrix. Enhanced plasma extraction of omarigliptin was successfully achieved with tertiary butyl methyl ether—diethyl ether (TBME-DEE) mixture as the extracting solvent, while using acetonitrile as the diluent solvent for the IS to effectively decrease the formed emulsion. Multiple Reaction Monitoring (MRM) of the transition pairs of m/z 399.2 to 153.0 for omarigliptin and m/z 340.2 to 116.0 for alogliptin was employed in positive Electro Spray Ionization (ESI) mode. Human plasma samples were collected after 1.5 h (tmax) of Marizev® (12.5 mg) tablets administration to healthy human volunteers showing average concentration of 292.18 nM. Validation results were all satisfactory including successful stability studies with bias below 12%. The proposed study will be valuable for ethnicity comparison studies that will be commenced on omarigliptin in Egypt by the authors in prospective study, following the FDA recommends, to evaluate possible sub-group dissimilarities that include pharmacokinetic parameters.

scholarly journals Bioanalytical Method Development and Validation of Memantine in Human Plasma by High Performance Liquid Chromatography with Tandem Mass Spectrometry: Application to Bioequivalence Study

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ravi Kumar Konda ◽  
B. R. Challa ◽  
Babu Rao Chandu ◽  
Kothapalli B. Chandrasekhar
Keyword(s):  
Human Plasma ◽  
High Performance ◽  
Method Development ◽  
Dynamic Range ◽  
Quantitative Estimation ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Bioequivalence Study ◽  
Healthy Human ◽  
Development And Validation

A simple, sensitive, and rapid HPLC-MS/MS method was developed and validated for quantitative estimation of memantine in human plasma. Chromatography was performed on Zorbax SB-C18(4.6×75 mm, 3.5 μm) column. Memantine (ME) and internal standard Memantine-d6(MED6) were extracted by using liquid-liquid extraction and analyzed by LC-ESI-MS/MS using multiple-reaction monitoring (MRM) mode. The assay exhibited a linear dynamic range of 50.00–50000.00 pg/ml for ME in human plasma. This method demonstrated an intra- and interday precision within the range of 2.1–3.7 and 1.4–7.8%, respectively. Further intra- and interday accuracy was within the range of 95.6–99.8 and 95.7–99.1% correspondingly. The mean recovery of ME and MED6 was86.07±6.87and80.31±5.70%, respectively. The described method was successfully employed in bioequivalence study of ME in Indian male healthy human volunteers under fasting conditions.

scholarly journals Development and validation of a rapid UHPLC-MS/MS method for the determination of fenofibric acid in human plasma: Application to a pharmacokinetic study of fenofibrate tablet in Chinese subjects

2020 ◽  
Author(s):  
Xiaorong Wu ◽  
Yankai Wang ◽  
Binbin Liang ◽  
Honghai Wu ◽  
Liying Wu ◽  
...  
Keyword(s):  
Human Plasma ◽  
Pharmacokinetic Study ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Fenofibric Acid ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Development And Validation ◽  
Chinese Subjects

AbstractAn ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method was developed to determine the fenofibric acid (FA) in human plasma and applied to a pharmacokinetic study of fenofibrate tablet (Lipanthyl® supra, 160 mg) on Chinese subjects which had not been reported. Bezafibrate was used as an internal standard (IS), and the plasma samples were precipitated by methanol. Multiple reaction monitoring (MRM) mode was used to quantitatively analyzed FA m/z 317.2 → 230.7 and the IS m/z 360.0 → 274.0 in the electrospray ionization (ESI) negative interface. The calibration curves were linear over the range of 50–30,000  ng/mL (r2  ≥  0.996). The intra-day and inter-day precision (coefficient of variation, CV%) was less than 2.7 and 2.5%, respectively. The accuracy (relative error, RE%) ranged from −4.5 to 6.9%. The average recovery was higher than 86.2%, and the matrix effect was between 95.32 and 110.55%. The simple, rapid, and selectivity method was successfully applied to the pharmacokinetic study of fenofibrate tablets on Chinese subjects.

scholarly journals Simultaneous Determination of Ropivacaine and 3-Hydroxy Ropivacaine in Cerebrospinal Fluid by UPLC-MS/MS

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Siyuan Chen ◽  
Jianshe Ma ◽  
Xianqin Wang ◽  
Quan Zhou
Keyword(s):  
Cerebrospinal Fluid ◽  
Extraction Efficiency ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Reaction Monitoring ◽  
Limit Of Quantification ◽  
Liquid Liquid Extraction ◽  
The Matrix ◽  
Interday Precision

In this paper, a UPLC-MS/MS method was developed for the determination of ropivacaine and its metabolite 3-hydroxy ropivacaine in cerebrospinal fluid. The cerebrospinal fluid was processed by ethyl acetate liquid-liquid extraction. The multiple reaction monitoring (MRM) mode was used for quantitative analysis by monitoring the transitions of m/z 275.3 → 126.2 for ropivacaine, m/z 291.0 → 126.0 for 3-hydroxy ropivacaine, and m/z 290.2 → 198.2 for the internal standard. Standard curves for ropivacaine and 3-hydroxy ropivacaine in cerebrospinal fluid were conducted over the concentration range of 0.2–2000 ng/mL, demonstrating excellent linearity, and the lower limit of quantification was 0.2 ng/mL. The intraday precision of ropivacaine and 3-hydroxy ropivacaine was less than 11%, while the interday precision was less than 7%. The accuracy ranged between 87% and 107%, the average extraction efficiency was higher than 79%, and the matrix effect was between 89% and 98%. The developed method was then applied to a case of suspected poisoning of ropivacaine.

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

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.

scholarly journals A Liquid Chromatography-Tandem Mass Spectrometry Method for Evaluation of Two Brands of Enalapril 20 mg Tablets in Healthy Human Volunteers

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Wael Abu Dayyih ◽  
Mohammed Hamad ◽  
Ahmad Abu Awwad ◽  
Eyad Mallah ◽  
Zainab Zakarya ◽  
...  
Keyword(s):  
Enzyme Inhibitor ◽  
Internal Standard ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Chronic Heart Disease ◽  
Chromatography Tandem Mass Spectrometry ◽  
Human Volunteers ◽  
Treatment Of Hypertension ◽  
Liquid Chromatography Tandem Mass ◽  
Enalapril And Enalaprilat

Enalapril is an angiotensin-converting enzyme inhibitor used for treatment of hypertension and chronic heart disease. Enalaprilat is its active metabolite responsible for the activity. This study aimed to develop and validate a method for enalapril and enalaprilat analysis and to determine the bioequivalence of two tablet formulae of enalapril. LC-MS/MS bioanalytical method was developed and validated and then applied to evaluate the bioavailability of two enalapril formulae. Antihyperglycemic sitagliptin was used as internal standard (IS). The method was accurate for the within- and between-days analysis, and precise CV% was <5%, being linear over the calibration range 1.0–200.0 ng/ml. Stability was >85% and the LOD was 0.907 and 0.910 ng/ml for enalapril and enalaprilat, respectively, and LLOQ was 1 ng/ml. The pharmacokinetic parameters Cmax, tmax, AUC0–72, and AUC0–∞ values of enalapril and enalaprilat of the two formulae were calculated and nonsignificant differences were found. A linearity, specific, accurate, and precise method was developed and applied for the analysis of enalapril and enalaprilat in human plasma after oral administration of two formulae of enalapril 20 mg tablets in healthy volunteers. Depending on the statistical analysis it was concluded that the two enalapril formulae were bioequivalent.

scholarly journals BIO-ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR THE SIMULTANEOUS ESTIMATION OF DECITABINE AND CEDAZURIDINE IN HUMAN PLASMA USING LC-MS/MS

2021 ◽  
pp. 257-262
Author(s):  
SAI PRUDHVI N. ◽  
VENKATESWARLU B. S. ◽  
KUMUDHAVALLI M. V. ◽  
MURUGANANTHAM V.
Keyword(s):  
Mass Spectrometry ◽  
Quality Control ◽  
Human Plasma ◽  
Method Development ◽  
Limit Of Detection ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Simultaneous Estimation ◽  
Limit Of Quantification ◽  
Validation Parameters

Objective: The present work aimed to develop a novel, reliable and accurate Liquid Chromatography-Mass Spectrometry/Mass spectrometry (LC-MS/MS) method for the simultaneous quantification of Decitabine and Cedazuridine a combined medication used for the treatment of chronic myelomonocytic leukemia in human plasma. Methods: Talazoparib drug is used as an internal standard in the study. Both the analytes and internal standard were isolated from 100 ml plasma samples by liquid-liquid extraction and then chromatographed on Zorbax SB-CN (4.6 mm×75 mm, 3.5 µm) column with a mobile phase consisting of 0.1 % ammonium formate and methanol in the ratio of 65:45 (v/v) pumped at 0.5 ml/min. The method had a chromatographic total run time of 5 min. Results: The developed method gave a symmetric peak at a retention time of 1.7 min for Decitabine, 2.2 min for Cedazuridine, 3.5 min for Talazoparib and satisfied all the peak properties as per USP guidelines. The mass spectral characterization of separated analytes in the LC method was performed using a mass detector operated at Multiple Reaction Monitoring mode with precursor-to-product ion transitions at m/z of 229 to m/z of 114 as MH+ion for Decitabine, m/z of 269 to m/z of 118 as MH+ion for Cedazuridine. A very sensitive limit of detection of 0.3 ng/ml was observed and showed a calibration curve linear over the concentration range of LLOQ (lower limit of quantification) to 500 ng/ml. The other validation parameters were found to have acceptable accuracy, precision, linearity, and selectivity. The mean extraction concentration was acceptable and very high for both the analytes in HQC (high-quality control concentration), MQC (medium quality control concentration) and LLOQ levels. The peak area response ratio of Decitabine and Cedazuridine with the internal standard in freeze-thaw, short term and long term stability studies was found to be acceptable confirms that the method is stable. Conclusion: It can be concluded that the proposed method is specific, accurate, and precise and could be used for the simultaneous estimation of Decitabine and Cedazuridine in human plasma.

Rapid, Sensitive and Simple LC-MS/MS Method Development and Validation for Estimation of Phenytoin in Human Plasma by using Deuterated Internal Standard

2021 ◽  
pp. 2937-2944
Author(s):  
Ajay I. Patel ◽  
Kishna Ram ◽  
Swati Guttikar ◽  
Amit Kumar J. Vyas ◽  
Ashok B. Patel ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Human Plasma ◽  
High Performance ◽  
Method Development ◽  
Dynamic Range ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Limit Of Quantification ◽  
Validation Parameters ◽  
Tandem Mass Spectrometric

A rapid, sensitive, accurate and precise high-performance liquid chromatography–tandem mass spectrometric (HPLC– MS/MS) method equipped with Electro Spray Ionization (ESI) source, operating in the Positive ion and Multiple Reaction Monitoring (MRM) mode was developed and validated for the estimation of Phenytoin in human plasma using Phenytoin D10 as an internal standard. Liquid-liquid extraction (LLE) technique was used to extract analyte and ISTDs from 0.2mL human plasma. The analytical separation was carried out in a reverse phase liquid chromatography by using C18 (150 x 4.6mm, 5µm) column, and 2mM Ammonium Acetate in water (pH 6.3): Methanol (30:70% v/v) mobile phase at 1mL/min in isocratic mode. Analytes were monitored in multiple reactions monitoring (MRM) mode using the respective [M+H]⁺ ions, m/z 253.10→ 182.30 for Phenytoin and m/z 263.30 → 192.20 for the internal standard, respectively. The Phenytoin and Phenytoin D10 retained at about 2.50 and 2.46 minutes respectively with total run time of 4 minute. The response of the LC-ESI-MS/MS method for both analyte and ISTD was linear over the dynamic range of 60-12000ng/mL with correlation coefficient r2 ≥ 0.9963. The Accuracy was well within the accepted limit of ± 20% at lower limit of quantification (LLOQ) and ± 15% at all the other concentrations in the linear range. Recovery of drug and ISTD was 87.52% and 86.42%, respectively. This method was fully validated for all the validation parameters and Stability studies. After optimization, the Bioanalytical method was validated according to USFDA, EMA and ANVISA guidelines for Bioanalysis.

AN LC-MS/MS BASED BIOANALYTICAL APPROACH TO RESOLVE PHARMACOKINETIC INVESTIGATION OF ACOTIAMIDE HYDROCHLORIDE AND ITS APPLICATION TO BIOEQUIVALENCE STUDY

2020 ◽  
pp. 76-84
Author(s):  
DHIMAN HALDER ◽  
SOURAV DAS ◽  
BALARAM GHOSH ◽  
EASHA BISWAS ◽  
SUKANTA ROY ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Bioequivalence Study ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Human Blood Plasma ◽  
Healthy Human ◽  
Clinical Phase ◽  
Prokinetic Drug

Objective: Acotiamide, a prokinetic drug used to treat Functional Dyspepsia, which acts by modulating gastric motility. However, in this present study, a simple and accurate bioanalytical method was developed for the estimation of Acotiamide in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and validated according to US-FDA guideline. Methods: The method was developed in blank human blood plasma; propranolol was used as internal standard (IS). Protein Precipitation technique was followed for the extraction of the drug from the plasma sample. In liquid chromatography, the C18 analytical column (50 x 3 mm, particle size-5 μm) was used; as a mobile phase, 0.1% formic acid in Mili Q water, and ACN with methanol (1:1) used, at 0.50 ml/min flow rate. Detection was done by positive electrospray ionization (ESI) with a run time of 7 min in multiple reaction monitoring (MRM) mode. Eight calibration concentrations were taken, ranging from 1.5625-200 ng/ml for Acotiamide. Different stability studies were performed and obtained results found within the acceptable range. Moreover, a comparative pharmacokinetic analysis was done in 24 healthy human volunteers in a single dose, randomized, crossover study. Results: The precursor to production reaction was; m/z 451.200 → 271.200 for Acotiamide and m/z 260.300 → 116.100 m/z for IS. The obtained calibration curve was linear, with a mean r2value 0.9953. Among the pharmacokinetic parameters, Cmax and Tmax were 25.71±2.31,23.61±2.32 ng/ml; 2.54±0.12, 2.43±0.21 h for reference and test samples, respectively. Conclusion: No major adverse events were noted in the clinical phase, the developed method was accurate and linear; obtained pharmacokinetic parameters hence represented.

scholarly journals Development and Validation of a LC/MS/MS Method for the Determination of Duloxetine in Human Plasma and Its Application to Pharmacokinetic Study

2012 ◽  
Vol 9 (2) ◽  
pp. 899-911 ◽  
Author(s):  
D. Chandrapal Reddy ◽  
A. T. Bapuji ◽  
V. Surayanarayana Rao ◽  
V. Himabindu ◽  
D. Rama Raju ◽  
...  
Keyword(s):  
Human Plasma ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Pharmacokinetic Parameters ◽  
Liquid Liquid Extraction ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Edta Plasma ◽  
Development And Validation

A selective, high sensitive and high throughput liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) method has been developed and validated for the chromatographic separation and quantitation of duloxetine in human EDTA plasma using fluoxetine (IS) as an internal standard. Analyte and IS were extracted from human plasma by liquid-liquid extraction using MTBE-n Hexane (80:20).The eluted samples were chromatographed on X-terra RP8 (50 mmx4.6 mm, 5 μm particle size) column by using mixture of 30 mM ammonium formate (pH-5.0±0.05) and acetonitrile as an isocratic mobile phase at a flow rate of 0.40 mL/min and analyzed by mass spectrometer in the multiple reaction monitoring (MRM) using the respective m/z 298.08→154.0 for duloxetine and 310.02→148.07 for IS. The linearity of the response/ concentration curve was established in human plasma over the concentration range 0.100-100.017 ng/mL. The lower detection limit (LOD,S/N>3) was 0.04 ng/mL and the lower limit of quantization (LOQ,S/N>10) was 0.100 ng/mL. This LC-MS/MS method was validated with Intra-batch and Inter-batch precision of 5.21-7.02. The Intra-batch and Inter-batch accuracy was 97.14-103.50 respectively. Recovery of duloxetine in human plasma is 80.31% and ISTD recovery is 81.09%. The main pharmacokinetic parameters were Tmax(hr) = (7.25±1.581), Cmax(ng/mL) (44.594±18.599), AUC0→t, = (984.702±526.502) and AUC0→∞, (1027.147±572.790) respectively.

scholarly journals Plasma Analysis of Celiprolol by HPTLC: A Useful Technique for Pharmacokinetic Studies

2001 ◽  
Vol 84 (4) ◽  
pp. 1252-1257 ◽  
Author(s):  
Hema S Savale ◽  
Kalpesh K Pandya ◽  
Thakorbhai P Gandhi ◽  
Indravadan A Modi ◽  
Rajiv I Modi ◽  
...  
Keyword(s):  
High Performance ◽  
Extraction Procedure ◽  
Internal Standard ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Healthy Human ◽  
Direct Estimate ◽  
Plasma Analysis ◽  
Human Volunteers ◽  
Simple Extraction

Abstract A rapid and sensitive high performance, thin-layer chromatographic (HPTLC) method has been developed for the measurement of celiprolol in human plasma and its use in pharmacokinetic studies has been evaluated. Detection and quantitation were performed without using an internal standard. A simple extraction procedure was followed for extracting celiprolol from plasma and a known amount of the extract was spotted on precoated silica gel 60 F254 plates using a Camag Linomat IV autosampler. Celiprolol was quantitated using a Camag TLC Scanner 3. The average recovery of authentic analytes (20 to 200 ng/mL) added to plasma was 72.06 ± 2.8% and the lowest amount of celiprolol that could be detected was 10 ng/mL. The method provides a direct estimate of the amount of celiprolol present in plasma. Pharmacokinetic parameters of 2 marketed preparations have also been determined after oral administration to 12 healthy human volunteers.

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