scholarly journals A Simple and Sensitive LC-MS/MS Method for Determination and Quantification of Potential Genotoxic Impurities in the Vismodegib Active Pharmaceutical Ingredient

2021 ◽  
pp. 88-102
Author(s):  
Rayala Rama Rao ◽  
Gundapaneni Ravi Kumar ◽  
Vadde Megha Vardhan ◽  
Veeraswami Boddu
Keyword(s):  
Mobile Phase ◽  
Multiple Reaction Monitoring ◽  
Active Pharmaceutical Ingredient ◽  
Mass Detection ◽  
Nitrobenzoic Acid ◽  
Genotoxic Impurities ◽  
Drug Sample ◽  
Multiple Reaction Monitoring Mode ◽  
Short Run ◽  
Gradient Mode

A rapid and sensitive LC-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative analysis of four potential genotoxic impurities Imp-A (2-chloro-5-nitroaniline), Imp-B (1-chloro-2-iodo-4-nitrobenzene), Imp-C (1-(2-chloro-5-nitrophenyl)ethan-1-one) and Imp-D (2-chloro-5-nitrobenzoic acid) in Vismodegib API drug sample. This trace analysis was achieved on CSH C18, 15.0 cm x 3.0 mm, 1.7 micron column maintained at 45°C. Optimal mobile phase consisted of 0.05% formic acid in water was used as mobile phase A and acetonitrile used as mobile phase B in gradient mode with the flow rate of 0.5 mL/min. The developed method had the short run time of 12 minutes. Quantification of four potential genotoxic impurities were carried out using mass detection with electrospray ionization in multiple reaction monitoring mode. The method was linear in the range of 0.03 ppm to 1.50 ppm for four potential genotoxic impurities with a correlation coefficient not less than 0.999. The recoveries were found satisfactory over the range between 96.67 and 106.90% for all selected impurities. The developed method was able to quantitate all four PGIs at a concentration level of 0.03 ppm (0.03 ppm with respect to 20 mg /mL Vismodegib).

scholarly journals A SELECTIVE AND SENSITIVE LC-MS/MS METHOD FOR QUANTIFICATION OF FOUR POTENTIAL GENOTOXIC IMPURITIES IN ATAZANAVIR SULFATE DRUG SUBSTANCE IN TRACE LEVEL

2021 ◽  
pp. 137-144
Author(s):  
SIVA JYOTHI N. ◽  
VENKATNARAYANA MUVVALA
Keyword(s):  
Mobile Phase ◽  
Multiple Reaction Monitoring ◽  
Research Work ◽  
Active Pharmaceutical Ingredient ◽  
Drug Substance ◽  
Genotoxic Impurities ◽  
Liquid Chromatography Tandem Mass ◽  
Short Run ◽  
Acquity Uplc ◽  
Atazanavir Sulfate

Objective: The main objective of current research work is to develop and validate a rapid, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the trace analysis of four potential genotoxic impurities in Atazanavir Sulfate drug substance. Methods: LC-MS/MS analysis of four potential genotoxic impurities was done on Acquity UPLC CSH C18 (100 mm × 2.1 mm, 1.7 μm) column. In this method, mobile phase A (10 mM ammonium acetate) mobile phase B (methanol: acetonitrile (90:10, v/v) with gradient run with the flow rate of 0.2 ml/min. The method was developed with the short run time of 13 min. Triple quadrupole mass detector coupled with positive electrospray ionization was used for the quantification of genotoxic impurities in multiple reaction monitoring (MRM) mode. Results: The method was linear in the range of 0.3 ppm to 4.5 ppm for BOC Hydrazine Acid impurity, BOC Epoxide and Keto impurity with a correlation coefficient not less than 0.9994. The accuracy of the method was in the range of 99.26% to 105.71% for all four potential genotoxic impurities (PGIs). No impurities were identified in the Atazanavir Sulfate active pharmaceutical ingredient sample. Conclusion: The proposed method is specific, linear, precise, accurate, robust and stable for the quantification of the four genotoxic impurities at very low levels.

scholarly journals Development and Validation of Three Potential Genotoxic Impurities by Liquid Chromatography Single Quad Mass Detector in Iomeprol

2021 ◽  
pp. 756-767
Author(s):  
Rayala Rama Rao ◽  
Gundapaneni Ravi Kumar ◽  
Vadde Megha Vardhan ◽  
Veeraswami Boddu
Keyword(s):  
Liquid Chromatography ◽  
Mobile Phase ◽  
Detection Method ◽  
Limit Of Detection ◽  
Gradient Elution ◽  
Mass Detection ◽  
Linear Calibration ◽  
Intermediate Precision ◽  
Relative Standard ◽  
Genotoxic Impurities

A liquid chromatography with single quadrupole mass detection method was developed for the determination of potential genotoxic impurities (PGIs) in the Iomeprol active pharmaceutical ingredient. Chromatographic separation was achieved on an Agilent Eclipse plus C8 column (100 mm x 2.1 mm x 1.8 μm) with 0.1% formic acid in water as mobile phase A and acetonitrile as mobile phase B in gradient elution mode at a 0.1 mL/min. Executed validation summary demonstrated that the mass detection method had highly sensitive and selective. A linear calibration curve (correlation coefficient, r> 0.999) was attained at the concentration range of 0.1-125 ppm for three PGI’s. The Limit of Detection of Imp-A, Imp-B and Imp-C in drug substance of Iomeprol is 0.05 ppm. The accuracy was confirmed by calculated recoveries (98.4-101.5%). The precision was tested at three levels: injection repeatability, analysis repeatability and intermediate precision. The calculated relative standard deviations were within the specification. The developed method was able to quantitate all three PGI’s at a concentration level of 1 µg/mL.

A Sensitive LC–MS/MS Method for the Determination of Afatinib in Human Plasma and Its Application to a Bioequivalence Study

2021 ◽  
Author(s):  
Xi Luo ◽  
Xiu Jin Zhang ◽  
Wen Ling Zhu ◽  
Jin Ling Yi ◽  
Wen Gang Xiong ◽  
...  
Keyword(s):  
Human Plasma ◽  
Mobile Phase ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Bioequivalence Study ◽  
Liquid Chromatography Tandem Mass ◽  
Multiple Reaction Monitoring Mode ◽  
Ionization Mode

Abstract A high performance liquid chromatography–tandem mass spectrometry assay for the determination of afatinib (AFT) in human plasma was established. A simple sample preparation of protein precipitation was used and separation was achieved on a C18 column by the gradient mixture of mobile Phase A of water (containing 0.1% ammonia) and the mobile Phase B of acetonitrile and water (V:V = 95:5, containing 0.2% ammonia). The multiple reaction monitoring mode was used to monitor the precursor-to-production transitions of m/z 486.2 → m/z 371.4 for AFT and m/z 492.2 → m/z 371.3 for AFT-d6 (internal standard) at positive ionization mode. The calibration curve ranged from 0.100 to 25.0 ng·mL−1 and the correlation coefficient was greater than 0.99. The intra- and inter-batch precision was less than or equal to 10.0%. Accuracy determined at four concentrations was in the range of 92.3–103.3%. In summary, our method was sensitive, simple and reliable for the quantification of AFT and was successfully applied to a bioequivalence study.

A Sensitive UPLC-MS/MS Method for the Determination of Flurbiprofen in Rat Plasma: Application to Real Sample

2021 ◽  
Author(s):  
Mehmet Emrah Yaman ◽  
Alptug Atila ◽  
Tugrul Cagri Akman ◽  
Mevlut Albayrak ◽  
Yucel Kadioglu ◽  
...  
Keyword(s):  
Retention Time ◽  
Mobile Phase ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
High Sensitivity ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Negative Ion ◽  
Linear Calibration ◽  
Multiple Reaction Monitoring Mode

Abstract For the quantification of flurbiprofen in rat plasma, a simple UPLC-MS/MS method with high sensitivity and short retention time for flurbiprofen was developed and validated using specific parameters. Etodolac was used as internal standard. The transitions (precursor to the product) of flurbiprofen and internal standard were obtained using the electrospray ionization in the negative ion multiple reaction monitoring mode, 243.2 → 199.2, 286.2 → 212.1, respectively. For chromatographic separation, C18 column was used for the stationary phase and gradient elution was used for the mobile phase. This mobile phase consisted of a methanol (A) and a 5 mM ammonium formate solution (B), which varied at a flow rate of 0.4 mL/min. For flurbiprofen, LLOQ was determined as 5 ng/mL. Quantification of flurbiprofen in the rat plasma with a linear calibration curve of 5–5000 ng/mL (r > 0.9991 for plasma) is possible with a retention time of 1.89 min. The total analysis time of the method was 3 min. The proposed method was validated. The intraday and inter-day precision (RSD%) and accuracy (RE%) were within 10% in all cases for flurbiprofen. The stability of flurbiprofen was evaluated under conditions such as short-term, long-term, autosampler and freeze/thaw. After method validation, flurbiprofen was succesfully quantified in real rat plasma samples.

scholarly journals Validation of a Method for the Determination of Chloramphenicol in Poultry and Swine Liver by Ultra-Performance Liquid Chromatography Coupled with Tandem Mass Spectrometry

2010 ◽  
Vol 93 (5) ◽  
pp. 1666-1671 ◽  
Author(s):  
Xi Xia ◽  
Xiaowei Li ◽  
Shuangyang Ding ◽  
Jianzhong Shen
Keyword(s):  
Liquid Chromatography ◽  
Mobile Phase ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Reaction Monitoring ◽  
Polymeric Sorbent ◽  
Multiple Reaction Monitoring Mode ◽  
Swine Liver

Abstract A sensitive and reliable method has been developed and validated for the determination of chloramphenicol in poultry and swine liver using SPE and ultra-performance liquid chromatography (UPLC)/MS/MS. The liver samples were extracted with ethyl acetate, defatted with n-hexane, and further cleaned up using SPE cartridges with polymeric sorbent. An Acquity BEH C18 column was used for gradient UPLC separation, with water and acetonitrile as the mobile phase. The multiple reaction monitoring mode was used for two precursor-product ion transitions for chloramphenicol and one for the internal standard. The method was validated at 0.1, 0.3, and 1.0 µg/kg. Mean recoveries from fortified samples ranged from 95.5 to 106.7% with an RSD of 12.2%. The method LOD was <0.02 µg/kg.

scholarly journals Low Level Determinations of Methyl Methanesulfonate and Ethyl Methanesulfonate Impurities in Emtricitabine Active Pharmaceutical Ingredient by LC/MS/MS using Electrospray Ionization

2011 ◽  
Vol 6 ◽  
pp. ACI.S6471 ◽  
Author(s):  
P.R. Kakadiya ◽  
T.G. Chandrashekhar ◽  
S. Ganguly ◽  
D.K. Singh ◽  
V. Singh
Keyword(s):  
Electrospray Ionization ◽  
Limit Of Detection ◽  
Multiple Reaction Monitoring ◽  
Active Pharmaceutical Ingredient ◽  
Case Method ◽  
Limit Of Quantification ◽  
Low Level ◽  
Quality Control Tool ◽  
Genotoxic Impurities

Alkyl methanesulfonates have been highlighted as potential genotoxic impurities (PGIs). A sensitive LC/MS/MS method was developed and validated for the determination of Alkyl methanesulfonate impurities in Emtricitabine API (active pharmaceutical ingredient). LC/MS/MS method on Zorbax SB C18 column (150 × 4.6 mm i.d.), 3.5 μm, with electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode was used. The proposed method was specific, linear, accurate, rugged and precise. The calibration curves showed good linearity over the concentration range of 0.0025 μg/ml to 0.3 μg/ml the correlation coefficient was >0.999 in each case. Method had very low limit of detection (LOD) and limit of quantification (LOQ) as 0.3 μg/g and 0.4 μg/g respectively for both the analytes. Accuracy was observed within 80%-120% for both the analytes. This method can be further extended a good quality control tool for low level quantitation of Alkyl methanesulfonate impurities in other API.

scholarly journals Development and validation of a reversed-phase HPLC method for determination of assay content of Teriflunomide by the aid of BOMD simulations

2021 ◽  
pp. 281-294 ◽  
Author(s):  
Abolghasem Beheshti ◽  
Zahra Kamalzadeha ◽  
Monireh Haj-Maleka ◽  
Meghdad Payaba ◽  
Mohammad Amin Rezvanfar ◽  
...  
Keyword(s):  
Mobile Phase ◽  
Potassium Dihydrogen Phosphate ◽  
Active Pharmaceutical Ingredient ◽  
Reversed Phase ◽  
Hplc Method ◽  
Dihydrogen Phosphate ◽  
Td Dft ◽  
High Level ◽  
Development And Validation

Due to the new hopes for treatment of multiple sclerosis (MS) diseases by Teriflunomide (TFN), in this project, a cheap, robust, and fully validated method has been developed both for determination of assay content in API (active pharmaceutical ingredient), and for related impurities analysis (RIA). To operate the method, a common C18, end-capped (250 × 4.6) mm, 5µm liquid chromatography column, was applied. The mobile phase A was prepared by dissolving 2.74 g (20mM) of PDP (potassium dihydrogen phosphate) and 3.72 g (50mM) of PC (potassium chloride) in water (1000 mL). Then, pH was adjusted to 3.0 by adding OPA (ortho-phosphoric acid) 85%; while, the mobile phase B was acetonitrile (ACN) (100%). In order to confirm the experimental data about the λmax of TFN, we have used the Born-Oppenheimer molecular dynamics (BOMD) simulations, quantum mechanics (QM), and TD-DFT calculations. According to the results, the method showed a high level of suitability, specificity, linearity, accuracy, precision, repeatability, robustness, and reliable detection limit.

scholarly journals Tyrosol and Hydroxytyrosol Determination in Extra Virgin Olive Oil with Direct Liquid Electron Ionization–Tandem Mass Spectrometry

Separations ◽  
2021 ◽  
Vol 8 (10) ◽  
pp. 173
Author(s):  
Veronica Termopoli ◽  
Maurizio Piergiovanni ◽  
Achille Cappiello ◽  
Pierangela Palma ◽  
Giorgio Famiglini
Keyword(s):  
Olive Oil ◽  
Matrix Effects ◽  
Multiple Reaction Monitoring ◽  
Virgin Olive Oil ◽  
Standard Addition ◽  
Extra Virgin Olive Oil ◽  
Electron Ionization ◽  
Free Form ◽  
Multiple Reaction Monitoring Mode ◽  
Health Promoting

Extra virgin olive oil (EVOO) is one of the main ingredients of the Mediterranean diet. It is claimed as a functional food for its unique content of health-promoting compounds. Tyrosol (Tyr), Hydroxytyrosol (Htyr), and their phenolic derivatives present in EVOO show beneficial properties, and their identification and quantification, both in their free form and after the hydrolysis of more complex precursors, are important to certify its quality. An alternative method for quantifying free and total Tyr and Htyr in EVOO is presented using an LC–MS interface based on electron ionization (EI), called liquid electron ionization (LEI). This method requires neither sample preparation nor chromatography; the sample is diluted and injected. The selectivity and sensitivity were assessed in multiple reaction monitoring mode (MRM), obtaining confirmation and quantification in actual samples ranging from 5 to 11 mg/Kg for the free forms and from 32 to 80 mg/Kg for their total amount after hydrolysis. Two MS/MS transitions were acquired for both compounds using the Q/q ratios as confirmatory parameters. Standard addition calibration curves demonstrated optimal linearity and negligible matrix effects, allowing a correct quantification even without expensive and difficult to find labeled internal standards. After several weeks of operation, the system’s repeatability was excellent, with an intraday RSD (%) spanning from five to nine and an interday RSD (%) spanning from 9 to 11.

scholarly journals METHOD DEVELOPMENT AND VALIDATION OF LERCANIDIPINE IN HUMAN PLASMA BY LIQUID CHROMATOGRAPHY TANDEM-MASS SPECTROMETRY

2018 ◽  
Vol 10 (4) ◽  
pp. 87
Author(s):  
Yahdiana Harahap ◽  
Norma Andriyani ◽  
Harmita .
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Method Development ◽  
Matrix Effects ◽  
Multiple Reaction Monitoring ◽  
Tandem Mass ◽  
Mass Detection ◽  
Column Temperature ◽  
Z Value

Objective: To obtain an optimum and validated method for analyzing lercanidipine in plasma using Ultra Performance Liquid Chromatography of Tandem Mass Spectrometry (UPLC-MS/MS).Methods: The separation was carried out using 1.7μm (2.1 x 100 mm) Waters AcquityTM UPLC C18 column, a mobile phase of the 0.1% formic acid-methanol mixture (20:80 v/v) with isocratic elution, 30 °C column temperature, 0.2 ml/min flow rate and amlodipine as an internal standard. Mass detection was performed with a positive XBL TQD type Electrospray Ionization (ESI) in Multiple Reaction Monitoring modes. Lercanidipine was detected at m/z value of 612.11>280.27 and amlodipine was detected at m/z value 409.1>238.15. The optimum sample preparation method was a liquid-liquid extraction using 5 ml of n-hexane-ethyl acetate (50:50 v/v), vortex mixed for 3 min, centrifuged at 4000 rpm for 20 min, evaporated with nitrogen at 50 °C for 30 min, and the residue was reconstituted with 100 μl of mobile phase.Results: The method was linear in the range of 0.025-10 ng/ml with r ≥ 0.9986. Accuracy and precision within-run and between-run met the requirements with %diff and %CV, not exceeding ± 15% and not more than ± 20% for Lower Limit of Quantification (LLOQ) concentration.Conclusion: It was concluded that the developed method met the requirements of selectivity, carry over, stability, the integrity of dilution, and matrix effects under the Guideline on Bioanalytical Method Validation by the European Medicines Agency in 2011. 

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