LC–MS/MS bioanalytical method for quantification of binimetinib and venetoclax, and their pharmacokinetic interaction

Bioanalysis ◽  
2021 ◽  
Author(s):  
Anuradha Reddy ◽  
Tarang Jadav ◽  
Amit Kumar Sahu ◽  
Pinaki Sengupta
Keyword(s):  
Therapeutic Strategy ◽  
Combined Treatment ◽  
Pharmacokinetic Interaction ◽  
Rat Plasma ◽  
Interaction Study ◽  
Bioanalytical Method ◽  
Anticancer Chemotherapy ◽  
Simultaneous Quantification ◽  
Study Results ◽  
Stability Results

Aim: Because of several prospective benefits, binimetinib (BMT)-venetoclax (VTC) combination can be a better therapeutic strategy to treat cancer. Results: An LC–MS/MS method for simultaneous quantification of BMT and VTC in rat plasma has been developed and validated. Specificity, accuracy, precision and stability results met the acceptance criteria for validation. Accuracy and precisions at all quality control levels were <15%. The study revealed that co-administration of BMT and VTC has no significant effect on their pharmacokinetics. Conclusion: The developed method can provide accurate results for quantification of BMT and VTC over the range of 5–500 ng/ml. The reported pharmacokinetic interaction study results will be useful for future consideration of the combined treatment of BMT and VTC in anticancer chemotherapy regimens.

High-throughput LC-MS/MS Method for Simultaneous Determination of Pantoprazole and Atorvastatin in Rat Plasma: Application to a Pharmacokinetic Interaction Study

2021 ◽  
Vol 22 ◽  
Author(s):  
Jian Le ◽  
Yuehua Liao ◽  
Shengni Li ◽  
Xiujuan Chen ◽  
Zhanying Hong
Keyword(s):  
Drug Interaction ◽  
Multiple Reaction Monitoring ◽  
Pharmacokinetic Interaction ◽  
Rat Plasma ◽  
Interaction Study ◽  
Triple Quadrupole Mass Spectrometer ◽  
Internal Standards ◽  
Spectrometric Data ◽  
Drug Drug Interaction

Background: Pantoprazole and atorvastatin are often used jointly in the clinic. The drug-drug interaction of pantoprazole and atorvastatin is worthy of being investigated. Objective: A highly rapid, sensitive, and selective LC-MS/MS method was developed for simultaneous quantification of pantoprazole and atorvastatin in rat plasma. Methods: Omeprazole and atorvastatin-d5 were used as the internal standards (ISs) of pantoprazole and atorvastatin, respectively. Simple protein precipitation was used to extract analytes from 50.0 μL plasma samples. Results: The chromatographic separation was achieved on a C18 column and the total chromatographic run time was 3.2 min. Acquisition of mass spectrometric data was performed on a triple-quadrupole mass spectrometer in multiple- reaction-monitoring (MRM) mode with an ESI source using the transition m/z 384→ 200 for pantoprazole and m/z 559.4→ 440.2 for atorvastatin, respectively. The method was validated over the concentration range of 20.0 ∼ 5000 ng/mL for pantoprazole and 1.00 ∼ 250 ng/mL for atorvastatin. All the validation results, including linearity, specificity, precision, accuracy, extraction recovery, matrix effect, and stability, met the acceptance criteria as per FDA guidelines. Conclusion: This method was successfully applied to a pharmacokinetic interaction study in Wistar rats. The results revealed significant evidence for the drug-drug interaction between pantoprazole and atorvastatin.

Simultaneous determination of Rivaroxaban and TAK-438 in rat plasma by LC–MS/MS: application to pharmacokinetic interaction study

Bioanalysis ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 11-22 ◽  
Author(s):  
Libin Wang ◽  
Shouchang Gai ◽  
Xiaorui Zhang ◽  
Xiaohui Xu ◽  
Nan Gou ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Internal Standard ◽  
Pharmacokinetic Interaction ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Interaction Study ◽  
Significant Difference ◽  
Us Fda ◽  
First Time

Aim: A sensitive and reliable LC–MS/MS method has been established and validated to the quantitation of rivaroxaban (RIV) and TAK-438 in rat plasma using carbamazepine as internal standard. Results: The procedure of method validation was conducted according to the guidelines of EMA and US FDA. At the same time, the method was applied to pharmacokinetic interactions study between RIV and TAK-438 for the first time. When RIV and TAK-438 co-administration to rats, main pharmacokinetic parameters of TAK-438 like AUC(0-t), AUC(0-∞) and Cmax had statistically significant increase. The main pharmacokinetic parameters of RIV have no statistically significant difference (p > 0.05) when co-administered except for t1/2 (p < 0.01). Conclusion: The results indicated that drug–drug interactions occurred between RIV and TAK-438 when co-administered to rats.

SFC-MS/MS method for simultaneous determination of nimodipine and 3-n-butylphthalide in beagle plasma: application to pharmacokinetic interaction study

Bioanalysis ◽  
2020 ◽  
Vol 12 (21) ◽  
pp. 1509-1519
Author(s):  
Weiping Wang ◽  
Pengyan Li ◽  
Mengna Fang ◽  
Xiaoting Li ◽  
Yu Zhang ◽  
...  
Keyword(s):  
High Throughput ◽  
Ammonium Acetate ◽  
Pharmacokinetic Interaction ◽  
Interaction Study ◽  
Isocratic Elution ◽  
Fda Guidance ◽  
Precipitation Procedure ◽  
Study Results ◽  
Us Fda

Aim: Nimodipine and 3-n-butylphthalide are co-administered to treat vascular dementia, but the pharmacokinetic interaction between the two drugs is still unknown. Therefore, a robust, high-throughput and economical supercritical fluid chromatography–ESI-MS/MS method has been initially developed to simultaneously determine nimodipine and 3-n-butylphthalide in beagle plasma, in order to study the safety of co-administration. Materials & methods: After a simple protein precipitation procedure, isocratic elution with mobile phase of CO2 and methanol (containing 0.3% formic acid and 2 mM ammonium acetate) was applied to minimize run time and facilitate sensitive and high-throughput bioanalysis. The method was fully validated according to US FDA Guidance. The validated method was then successfully applied in a pharmacokinetic interaction study. Results: The results indicated there is no significant pharmacokinetic interaction between the two drugs.

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