scholarly journals Validated LC-ESI-MS/MS method for the determination of ivosidenib in 10 µL mice plasma: application to a pharmacokinetic study

ADMET & DMPK ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 131-139 ◽  
Author(s):  
Sreekanth Dittakavi ◽  
Rakesh Kumar Jat ◽  
Sadanand Rangnathrao Mallurwar ◽  
Ravi Kumar Jairam ◽  
Ramesh Mullangi
Keyword(s):  
Pharmacokinetic Study ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Precipitation Process ◽  
Esi Ms ◽  
Accuracy And Precision ◽  
Multiple Reaction Monitoring Mode ◽  
Positive Ion ◽  
Regulatory Guideline

A simple, selective and rapid LC-ESI-MS/MS method has been developed and validated for the quantification of ivosidenib in mice plasma using warfarin as an internal standard (I.S.) as per regulatory guideline. Sample preparation was accomplished through a simple protein precipitation process. Chromatography of ivosidenib and the I.S. was achieved on an Atlantis dC18 column using an isocratic mobile phase comprising 0.2 % formic acid in water and acetonitrile (25:75, v/v) delivered at a flow rate of 1.0 mL/min. LC-MS/MS was operated under the multiple reaction-monitoring mode (MRM) using the electrospray ionization technique in positive ion mode and the transitions of m/z 583.1→186.1 and m/z 309.2→251.3 were used to quantitate ivosidenib and the I.S, respectively. The total chromatographic run time was 2.0 min. Linearity was established in the concentration range of 1.10-3293 ng/mL (r2>0.99). The intra- and inter-day accuracy and precision for ivosidenib in mice plasma were in the range of 5.72-9.91 and 5.90-10.7 %, respectively. Ivosidenib was found to be stable on bench-top for 6 h, up to three freeze-thaw cycles, in in-injector for 24 h and for one month at -80 °C. The applicability of the validated method has been demonstrated in a mice pharmacokinetic study. Following intravenous (2 mg/kg) and oral (5 mg/kg) administration of ivosidenib to mice, concentrations were quantifiable up to 24 and 48 h, respectively. The bioavailability was 61 %.

Determination of Tofacitinib in Mice Whole Blood on Dried Blood Spots Using LC–ESI–MS/MS: Application to Pharmacokinetic Study in Mice

Drug Research ◽  
2018 ◽  
Vol 69 (06) ◽  
pp. 330-336 ◽  
Author(s):  
Abhishek Dixit ◽  
Sadanand Rangnathrao Mallurwar ◽  
Suresh P Sulochana ◽  
Mohd Zainuddin ◽  
Ramesh Mullangi
Keyword(s):  
Pharmacokinetic Study ◽  
Whole Blood ◽  
Internal Standard ◽  
Dried Blood Spots ◽  
Assay Method ◽  
Blood Spots ◽  
Novel Method ◽  
Positive Ion ◽  
Regulatory Guideline

AbstractA simple, sensitive and rapid assay method has been developed and validated as per regulatory guideline for the estimation of tofacitinib on mice dried blood spots (DBS) using liquid chromatography coupled to tandem mass spectrometry with electro spray ionization in the positive-ion mode. The method employs liquid extraction of tofacitinib from DBS disk of mice whole blood followed by chromatographic separation using 5 mM ammonium acetate (pH 6.5):acetonitrile (20:80, v/v) at a flow rate of 0.60 mL/min on an X-Terra Phenyl column with a total run time 2.5 min. The MS/MS ion transitions monitored were m/z 313→149 for tofacitinib and m/z 316→149 for the internal standard (13C3, 15N-tofacitinib). The assay was linear in the range of 0.99–1980 ng/mL. The intra- and inter-day precision was in the range of 1.17–10.3 and 3.37–10.9%, respectively. Stability studies showed that tofacitinib was stable on DBS cards for one month. This novel method has been applied to analyze the DBS samples of tofacitinib obtained from a pharmacokinetic study in mice.

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

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.

DBS Assay with LC-MS/MS for the Determination of Idelalisib, A Selective PI3K-δ Inhibitor in Mice Blood and Its Application to a Pharmacokinetic Study

Drug Research ◽  
2020 ◽  
Vol 71 (01) ◽  
pp. 36-42
Author(s):  
Harsha K. Tripathy ◽  
Nair S.V. Manju ◽  
Sreekanth Dittakavi ◽  
Ashok Zakkula ◽  
Ramesh Mullangi
Keyword(s):  
Pharmacokinetic Study ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Lymphocytic Leukemia ◽  
Extraction Solvent ◽  
Non Hodgkin Lymphoma ◽  
Validation Parameters ◽  
Multiple Reaction Monitoring Mode ◽  
Carry Over

AbstractIdelalisib is a selective and second-generation PI3K-δ inhibitor, approved for the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia. In this paper, we present a fully validated dried blood spot (DBS) method for the quantitation of idelalisib from mice blood using an LC-MS/MS, which was operated under multiple reaction monitoring mode. To the punched DBS discs, acidified methanol enriched with internal standard (IS; larotrectinib) was added and extracted using tert-butyl methyl ether as an extraction solvent with sonication. Chromatographic separation of idelalisib and the IS was achieved on an Atlantis dC18 column using a mixture of 10 mM ammonium formate:acetonitrile (25:75, v/v). The flow-rate and injection volume were 0.80 mL/min and 2.0 µL, respectively. Idelalisib and the IS were eluted at ~0.98 and 0.93 min, respectively and the total run time was 2.00 min. Idelalisib and the IS were analyzed using positive ion scan mode and parent-daughter mass to charge ion (m/z) transition of 416.1→176.1 and 429.1→342.1, respectively was used for the quantitation. The calibration range was 1.01−4 797 ng/mL. No matrix effect and carry over were observed. Haematocrit did not influence DBS idelalisib concentrations. All the validation parameters met the acceptance criteria. The applicability of the validated method was shown in a mice pharmacokinetic study.

HPLC/Tandem Mass Spectrometric Studies on Steroidal Saponins: An Example of Quantitative Determination of Shatavarin IV from Dietary Supplements Containing Asparagus racemosus

2014 ◽  
Vol 97 (6) ◽  
pp. 1497-1502 ◽  
Author(s):  
Dada Patil ◽  
Manish Gautam ◽  
Sunil Gairola ◽  
Suresh Jadhav ◽  
Bhushan Patwardhan
Keyword(s):  
Acetic Acid ◽  
Dietary Supplements ◽  
Quantitative Estimation ◽  
Multiple Reaction Monitoring ◽  
Asparagus Racemosus ◽  
Steroidal Saponin ◽  
Esi Ms ◽  
Tandem Mass Spectrometric ◽  
Positive Ion

Abstract Asparagus racemosus (AR) is a popular botanical present in several Ayurvedic medicines and nutritional and dietary supplements with immunomodulatory, galactogogue, and anticancer activity. A steroidal saponin known as shatavarin IV is one of the active constituents of AR. A new, selective, and rapid HPLC/MS/MS method has been developed and validated for quantitative estimation of shatavarin IV in crude, processed, and marketed samples of AR. The analytes were separated on a Luna C18 column using simple isocratic elution with water (0.1% acetic acid)–acetonitrile (0.1% acetic acid; 70 + 30, v/v) at a flow rate of 0.8 mL/min. The analytes were detected by electrospray ionization (ESI)-MS/MS and quantified using multiple reaction monitoring techniques in the positive ion mode. The method showed excellent linearity (r2 > 0.998) over the concentration range of 7.5 to 254 ng/mL with LOD of 2.5 ng/mL. Precision (RSD) and accuracy (recovery) were found in the ranges of 2.00 to 5.15 and 102 to 110%, respectively. The validated HPLC/ESI-MS/MS method was successfully applied to the quantification of shatavarin IV in crude, processed, and marketed (single or multiherb) AR samples. Therefore, this method could be used for QC and standardization of pharmaceutical or nutritional products containing AR.

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

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Renjie Xu ◽  
Mengyue Wang ◽  
Ying Peng ◽  
Xiaobo Li
Keyword(s):  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Sprague Dawley ◽  
Ionization Source ◽  
Fragment Ions ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Positive Ion

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.

scholarly journals A Rapid and Selective LC-MS/MS Method for Quantification of Quetiapine in Human Plasma and its Application to Pharmacokinetic Study on Indian Schizophrenia Patients

2011 ◽  
Vol 8 (4) ◽  
pp. 1802-1814 ◽  
Author(s):  
S. Ravinder ◽  
A. T. Bapuji ◽  
K. Mukkanti ◽  
M. Nagesh ◽  
H. L. V. Ravikiran
Keyword(s):  
Mass Spectrometry ◽  
Human Plasma ◽  
Pharmacokinetic Study ◽  
Dynamic Range ◽  
Solid Phase ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Plasma Samples ◽  
Standard Curve ◽  
Multiple Reaction Monitoring Mode

A rapid, robust and selective high pressure liquid chromatography–positive electrospray ionization tandem mass spectrometry method has been developed and validated for the quantification of quetiapine (QUE) in human plasma with K2EDTA using oxcarbazepine (IS) as an internal standard. Analyte and internal standard were extracted from human plasma by solid-phase extraction using acetonitrile. The eluted samples were chromatographed on a C18 column by using a 10:75:15v/v mixture of ammonium formate buffer (5 mM, pH 4.50) and acetonitrile and methanol as an isocratic mobile phase at a flow rate of 0.4 mL/min and analyzed by mass spectrometry in the multiple reaction monitoring mode using the respective [M+H]+ions,m/z384.3/253.2 for Quetiapine andm/z253.1/208.1 for the internal standard. The assay exhibited a linear dynamic range of 5.01 - 2501.04 ng/mL for quetiapine in human plasma. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.5 min for each sample made it possible to analyze 300 patient plasma samples per day. The validated method has been successfully used for the estimation of quetiapine in real time schizophrenia patient’s plasma samples for pharmacokinetic study.

scholarly journals Development and Validation of an HPLC-MS/MS Method for Rapid Simultaneous Determination of Cefprozil Diastereomers in Human Plasma

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Guodong He ◽  
Liping Mai ◽  
Xipei Wang
Keyword(s):  
Mass Spectrometry ◽  
Antimicrobial Activity ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Reaction Monitoring ◽  
Reverse Phase ◽  
Development And Validation ◽  
Positive Ion ◽  
Sensitive Method

Background. Both cis- and trans-cefprozil have antimicrobial activity, but their potencies are quite different. It is therefore necessary to develop a sensitive method to simultaneously determine both isomers for pharmacokinetic and bioequivalence studies. Methods. An LC-MS/MS method, using stable isotope-labeled cefprozil as the internal standard, was developed and validated. The analytes were extracted from plasma by protein precipitation and separated on a reverse-phase C18 column using a gradient program consisting of 0.5% formic acid and acetonitrile within 4 min. The mass spectrometry acquisition was performed with multiple reaction monitoring in positive ion mode using the respective [M+H]+ ions, m/z 391.2→114.0 for cefprozil and 395.0→114.5 for cefprozil-D4. Results. The calibration curves were linear over the ranges of 0.025–15 μg/mL for cis-cefprozil and 0.014–1.67 μg/mL for trans-cefprozil. The accuracies for the cis and trans isomers of cefprozil were 93.1% and 103.0%, respectively. The intra- and interassay precisions for the QC samples of the isomers were < 14.3%. The intra- and interassay precisions at the LLOQ were < 16.5%. Conclusions. The method was sensitive and reproducible and was applied in a pilot pharmacokinetic study of healthy volunteers.

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

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1403 ◽  
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.

scholarly journals Development and Validation of an HPLC-UV Detection Assay for the Determination of Clonidine in Mouse Plasma and Its Application to a Pharmacokinetic Study

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4109
Author(s):  
Haitham AlRabiah ◽  
Sabry M. Attia ◽  
Nasser S. Al-Shakliah ◽  
Gamal A. E. Mostafa
Keyword(s):  
Pharmacokinetic Study ◽  
Limit Of Detection ◽  
Internal Standard ◽  
Reversed Phase ◽  
Linear Calibration ◽  
Mouse Plasma ◽  
Accuracy And Precision ◽  
Detection Assay ◽  
Development And Validation

An accurate and simple HPLC-UV method has been developed for the determination of clonidine in mouse plasma. A reversed phase C18 Nova Pack® column (125 mm × 4.6 mm i.d., × 3 μm particle size) was used as stationary phase. The mobile phase composition was a mixture of 0.1% diethylamine/acetonitrile (70:30, v/v) at pH 8 in an isocratic mode at flow rate was 1.0 mL/min. Detection was set at 210 nm. Tizanidine was used as an internal standard. The clonidine and tizanidine were extracted from plasma matrix using the deproteinization technique. The developed method exhibited a linear calibration range 100.0–2000 ng/mL and the lower limit of detection (LOD) and quantification (LOQ) were 31.0 and 91.9 ng/mL, respectively. The intra-day and inter-day accuracy and precision of the method were within 8.0% and 3.0%, respectively, relative to the nominal concentration. The developed method was validated with respect to linearity, accuracy, precision, and selectivity according to the US Food and drug guideline. Minimal degradation was demonstrated during the determination of clonidine under different stability conditions. The suggested method has been successfully applied during a pharmacokinetic study of clonidine in mouse plasma.

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