Simultaneous Estimation of Genotoxic Impurities 4-Nitrobenzene Trifluoride, 4-Aminobenzene Trifluoride, and Benzo Trichloride in Cinacalcet Hydrochloride by GC-MS/MS Method

2021 ◽  
Vol 14 (6) ◽  
pp. 5691-5707
Author(s):  
Ravichandrababu Rupakula ◽  
Suman Gundlapalli
Keyword(s):  
Mass Spectrometry ◽  
Limit Of Detection ◽  
Ion Source ◽  
Gas Chromatography Mass Spectrometry ◽  
Interface Temperature ◽  
Simultaneous Estimation ◽  
Control Analysis ◽  
Ich Guidelines ◽  
Genotoxic Impurities ◽  
Cinacalcet Hydrochloride

The main objective of this study is to develop and validate a novel, fast, and more sensitive gas chromatography-mass spectrometry (GC-MS/MS) method for the simultaneous estimation of 4-Nitrobenzotrifluoride (4-NBTF), 4-Amino-benzotrifluoride (4-ABTF), and Benzotrichloride (BTC) impurities in Cinacalcet hydrochloride (CH). The chromate-graphic separations were performed on a DB-624, 30m × 0.32mm × 1.8µm column with injector temperature of 150°C, and mode of injection is split with asplit ratio 1: 20. The carrier gas used was helium with a flowrate 1.5 mL/min, and theinjection load was 1.0 µL. Mass spectrometry quantitation was achieved by aquadrupole analyser with EI (Electron Ionization) ion source atasource temperature of 250ºC and interface temperature of 250ºC. The retention times for 4-NBTF, 4-ABTF, and BTC were at 6.13, 6.74and 7.64min, respectively. The calibration curve was linear over the concentration ranging from LOQ level to 150 % level with the correlation coefficient (r) of > 0.99. The percentage recovery was found to be within the specified range, i.e., 70.0 to 130.0 for the three impurities. The limit of detection (LOD) was established to 0.19, 0.19, and 0.18 ppm, whereas thelimit of quantification (LOQ) was obtained to 1.14, 1.12, and 1.11 ppm for 4-NBTF, 4-ABTF, and BTC, respectively. The test solutions with impurities were found to be stable in the diluent for 24 hours. A simple GC-MS/MS method was developed and validated for simultaneous estimation of three impurities in CH. The method was accurate, precise, linear, specific, sensitive, robust, and rugged as per ICH guidelines. The method has been applied to the real-time batch analysis and found to be suitable for routine quality control analysis of CH. 

scholarly journals UV Spectrophotometric Methods to Quantify Alogliptin Benzoate and Pioglitazone Hydrochloride

2021 ◽  
pp. 31-41
Author(s):  
Dhanya B. Sen ◽  
Ashim K. Sen ◽  
Aarti S. Zanwar ◽  
Harshita Pandey ◽  
Rajesh A. Maheshwari
Keyword(s):  
Limit Of Detection ◽  
Spectroscopic Method ◽  
Simultaneous Estimation ◽  
Control Analysis ◽  
Limit Of Quantification ◽  
Spectrophotometric Methods ◽  
First Derivative ◽  
Ich Guidelines ◽  
The Difference ◽  
Tablet Dosage

Three new, precise, accurate and sensitive UV-Spectrophotometric methods namely Ratio Difference Spectroscopic Method (RDSM), First Derivative of Ratio Spectra Method (DR1) and Area Under Curve Method (AUC) were developed and validated for simultaneous assessment of alogliptin benzoate (ALO) and pioglitazone hydrochloride (PIO) in tablet dosage form. In RDSM, ratio spectra of both the drugs were recorded by dividing the mixtures using interfering drug as divisor. Then the difference between the amplitudes of obtained ratio spectra was measured at 288 and 291 nm for ALO and 236 and 245 nm for PIO. The second method DR1, where the first derivative of ratio spectra of both the drugs were recorded and the first derivative signal was measured at 290 nm for ALO and 276.8 nm for PIO. The scaling factor was fixed as 1 and wavelength interval (Δλ) as 2 for recording the first derivative of ratio spectra.  In the third method (AUC), peak area of recorded zero order spectra was measured at 276 ± 10 nm for ALO and 267.8 ± 10 nm for PIO. All three proposed methods were validated according to “International Conference on Harmonization” (ICH) guidelines parameters. For all three methods, ALO and PIO obeyed Beer’s law in the range of 0.5-5 & 1.8-18 µg/ml, respectively. The % RSD of repeatability of measurement, intra-day and inter-day precision were found to be less than 2 for all three methods. Limit of detection (LOD) and Limit of quantification (LOQ) of the drugs were calculated which proved the sensitivity of the methods. The accuracy ranged between 98-101% for all three methods. No interference from pharmaceutical excipients present in the formulation was observed.  These proposed methods were found to be simple, sensitive, accurate and precise and can be applied to the simultaneous estimation of ALO and PIO in combined tablet formulation and also appropriate for routine quality control analysis.

RP-HPLC METHOD FOR ESTIMATION OF LORNOXICAM IN TABLETS AND IN DISSOLUTION SAMPLES USING MASS SPECTROMETRIC COMPATIBLE BUFFERS

INDIAN DRUGS ◽  
2021 ◽  
Vol 58 (07) ◽  
pp. 32-37
Author(s):  
Vijaya Lakshmi Marella ◽  
Chaitanya S. N ◽  
Keyword(s):  
High Performance ◽  
Limit Of Detection ◽  
High Performance Liquid Chromatographic ◽  
Hplc Method ◽  
Mass Spectrometric ◽  
Control Analysis ◽  
Limit Of Quantification ◽  
Pharmaceutical Dosage Forms ◽  
Ich Guidelines ◽  
Liquid Chromatographic

A selective and sensitive reverse phase High Performance Liquid Chromatographic method has been developed and validated for the estimation of lornoxicam in bulk, pharmaceutical dosage forms and in dissolution samples. The analysis was performed isocratically on an Inertsil column (250* 4.6 mm, 5 µm) using a mass spectrometric compatible mobile phase of 10 mM ammonium acetate: acetonitrile (50:50 V/V) at a flow rate of 1 mL/min.The detection wavelength was 290 nm. The retention time was found to be 4.573 min for lornoxicam. The linearity of the method has been satisfied with Beer Lambert’s law in the concentration range of 5-25 µg/mL with a correlation coefficient of 0.9988. The mean recoveries assessed for lornoxicam were in the range of 100.39-101.86 %, indicating good accuracy of the method. The limit of detection and limit of quantification were found to be 0.03 and 0.11 µg/mL, respectively. The developed method has been statistically validated in accordance with ICH guidelines and found to be mass spectrometric compatible, simple, precise, and accurate with the prescribed values. Thus, the proposed method was successfully applied for the estimation of lornoxicam in routine quality control analysis of bulk, formulations and in dissolution samples.

Development and Validation of the Analytical method for the estimation of a combination of 5-fluorouracil and Imiquimod by RP-HPLC

2021 ◽  
pp. 3313-3318
Author(s):  
Bhupender Tomar ◽  
Ankita Sharma ◽  
Inder Kumar ◽  
Sandeep Jain ◽  
Pallavi Ahirrao
Keyword(s):  
High Performance ◽  
Limit Of Detection ◽  
High Performance Liquid Chromatographic ◽  
Simultaneous Estimation ◽  
Limit Of Quantification ◽  
Pharmaceutical Ingredients ◽  
Rp Hplc ◽  
Ich Guidelines ◽  
Development And Validation ◽  
Liquid Chromatographic

A simple, precise, and accurate reverse phase high performance liquid chromatographic method (RP-HPLC) was developed and validated for the estimation of the combination of 5- Fluorouracil (5-FU) and Imiquimod in active pharmaceutical ingredients (APIs). The method was carried out on Phenomenex C18 (250 × 4.6mm I.D., 5𝜇m) using isocratic elution mode. The mobile phase was used as Acetonitrile: 10mM potassium dihydrogen orthophosphate: triethylamine (40:59.9:0.1, v/v, pH 4.5 with orthophosphoric acid) and Water: ACN (50:50 v/v) was used as a diluent. The concentration of solvents was 1-20µg/ml and the volume of injection was 20µl with the flow rate of 1.2ml/min. The retention times for 5-FU and Imiquimod were found to be 1.9±0.5 and 6.6±0.5 min respectively. The absorption maxima of 5FU and Imiquimod were found 267nm and 227nm respectively. The method was validated as per ICH guidelines. All the data were found within the specified limits. The limit of detection (LOD) and limit of quantification (LOQ) of 5- Fluorouracil were found to be 0.015μg/mL and 0.048 μg/mL, respectively, and Imiquimod was found to be 0.078μg/mL and 0.237μg/mL, respectively. The method developed in the present study was found to be sensitive, specific, and precise and can be applied for the simultaneous estimation of 5-FU and Imiquimod.

Simultaneous Determination of Alachlor, Metolachlor, Atrazine, and Simazine in Water and Soil by Isotope Dilution Gas Chromatography/Mass Spectrometry

1989 ◽  
Vol 72 (2) ◽  
pp. 349-354 ◽  
Author(s):  
Lee Q Huang
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Simultaneous Determination ◽  
Isotope Dilution ◽  
Limit Of Detection ◽  
Solid Phase ◽  
Gas Chromatography Mass Spectrometry ◽  
Selected Ion Monitoring ◽  
Chromatography Mass Spectrometry

Abstract A multiresidue method was developed for the simultaneous determination of low parts per billion (ppb) concentrations of the herbicides alachlor, metolachlor, atrazine, and simazine in water and soil using isotope dilution gas chromatography/mass spectrometry (GC/MS). Known amounts of 15N,13C-alachlor and 2H5-atrazine were added to each sample as internal standards. The samples were then prepared by a solid phase extraction with no further cleanup. A high resolution GC/low resolution MS system with data acquisition in selected ion monitoring mode was used to quantitate herbicides in the extract. The limit of detection was 0.05 ppb for water and 0.5 ppb for soil. Accuracy greater than 80% and precision better than 4% was demonstrated with spiked samples.

Determination of Phytosterols in Butter Samples by Using Capillary Column Gas Chromatography

1987 ◽  
Vol 70 (5) ◽  
pp. 912-915 ◽  
Author(s):  
Randall L Smith ◽  
Darryl M Sullivan ◽  
Earl F Richter
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Retention Time ◽  
Capillary Column ◽  
Limit Of Detection ◽  
Packed Column ◽  
Gas Chromatography Mass Spectrometry ◽  
Positive Bias ◽  
Capillary Column Gas Chromatography

Abstract A positive bias in the gas chromatographic (GC) analysis of butter for β-sitosterol was discovered when attempting to confirm values by gas chromatography/mass spectrometry (GC/MS). The source of the problem was traced to an interfering material that was not effectively separated by packed column GC. Because capillary columns are known to provide superior separation, they were substituted for packed columns in the assay, and instrument parameters were modified accordingly. A compound with a similar retention time, identified by GC/MS as lanosterol, was separated from β-sitosterol by the capillary column. The capillary column technique was applied to over 300 butter samples. The results indicate that the method can accurately quantitate β-sitosterol in butter with no known interferences. The limit of detection for this method is 1 mg/100 g. Recoveries at a level of 3 mg/100 g averaged 98% with a coefficient of variation of 3.45%

scholarly journals Simultaneous Estimation and Validation of Atorvastatin Calcium and Aspirin in Combined Capsule Dosage Form by RP HPLC Method

2012 ◽  
Vol 9 (3) ◽  
pp. 1449-1456
Author(s):  
B. V. Suma ◽  
K. Kannan ◽  
V. Madhavan ◽  
Chandini R. Nayar
Keyword(s):  
Limit Of Detection ◽  
Hplc Method ◽  
Simultaneous Estimation ◽  
Uv Detector ◽  
Limit Of Quantification ◽  
Chromatography Method ◽  
Atorvastatin Calcium ◽  
Ich Guidelines ◽  
Phase Liquid ◽  
Liquid Chromatography Method

A new simple, specific, precise and accurate revere phase liquid chromatography method has been developed for estimation of atorvastatin calcium (AST) and ASPIRIN (ASP) simultaneously in a combined capsule dosage forms. The chromatographic separation was achieved on a 5 – micron C 18 column (250x 4.6mm) using a mobile phase consisting of a mixture of Acetonitrile: Ammonium Acetate buffer 0.02M (68:32) pH 4.5. The flow rate was maintained at 0.8 ml/min. The detection of the constituents was done using UV detector at 245 nm for AST and ASP. The retention time of AST and ASP were found be 4.5915 ± 0.0031 min and 3.282 ±0.0024 min respectively. The developed method was validated for accuracy, linearity, precision, limit of detection (LOD) and limit of quantification (LOQ) and robustness as per the ICH guidelines.

Determination of ketamine and norketamine in hair and evaluation of polydrug use in ketamine abusers using hair analysis in Korea

2020 ◽  
Author(s):  
Jongsook Rhee ◽  
Jihyun Kim ◽  
Moonhee Jang ◽  
Ilchung Shi ◽  
Sangki Lee
Keyword(s):  
Mass Spectrometry ◽  
Matrix Effects ◽  
Limit Of Detection ◽  
Gas Chromatography Mass Spectrometry ◽  
Controlled Drugs ◽  
Hair Samples ◽  
Limit Of Quantitation ◽  
Liquid Chromatography Tandem Mass ◽  
Forensic Service

Abstract This study evaluated hair samples from 28 subjects who had measurable ketamine levels among the samples requested from 2016 to 2017 into Seoul Institute National Forensic Service in Korea. Ketamine in the hair was extracted by using a solution of 1% hydrochloric acid in methanol for 16 h. Extracts were analyzed using gas chromatography mass spectrometry (GC-MS) or liquid chromatography tandem mass spectrometry (LC-MS-MS). LC-MS-MS method was validated by determining the limit of detection (LOD), limit of quantitation (LOQ), linearity, intra- and inter-accuracy, precision, and matrix effects. In 59 ketamine-positive hair or hair segments from 28 ketamine abusers, the ketamine concentration was found to be in the range of 0.011-335.8 ng/mg (mean, 13.6; median, 1.8), and the norketamine concentration was found to be in the range of 0.001-35.7 ng/mg (mean, 7.5; median, 0.44). The ratio of norketamine to ketamine concentration in hair was in the range of 0.01-1.46 (mean, 0.34; median, 0.26). The distribution of ketamine concentration in hair samples was as follows: 0.01-0.1 ng/mg in 11 samples (18.6%), 0.1-5 ng/mg in 33 samples (55.9%), 5-10 ng/mg in 4 samples (6.8%), 10-15 ng/mg in 2 samples (3.4%), 15-20 ng/mg in 4 samples (6.8%), 40-45 ng/mg in 2 samples (3.4%), 45-50 ng/mg in 1 samples 1.7%) and >100 ng/mg in only 2 samples (3.4%). In the hair of ketamine-abusers, 26 of 28 subjects had simultaneously ketamine with detectable levels of other controlled drugs, including MDMA (n=9), MA (n=3), MDMA/MA (n=3), MDMA/PMA (n=3), MDMA/PMA/MA (n=2), cocaine (n=1), and other drugs (n=5, propofol, zolpidem or benzodiazepines). In most of the hair samples were detected ketamine with other controlled drugs: MDMA (60.7%), MA (28.6%), PMA(17.9%), zolpidem (17.9%), and propofol (14.3%) in the frequency of abuse. In conclusion, most of the ketamine-abusers (92.9%) would be polydrug abusers, who were concomitantly abusing other controlled substances.

scholarly journals Development of Sensitive and Specific Analysis of Vildagliptin in Pharmaceutical Formulation by Gas Chromatography-Mass Spectrometry

2015 ◽  
Vol 2015 ◽  
pp. 1-7
Author(s):  
Ebru Uçaktürk
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Limit Of Detection ◽  
Internal Standard ◽  
Pharmaceutical Formulation ◽  
Gas Chromatography Mass Spectrometry ◽  
Selected Ion Monitoring ◽  
Chromatography Mass Spectrometry ◽  
Validation Parameters ◽  
Diagnostic Ions

A sensitive and selective gas chromatography-mass spectrometry (GC-MS) method was developed and fully validated for the determination of vildagliptin (VIL) in pharmaceutical formulation. Prior to GC-MS analysis, VIL was efficiently derivatized with MSTFA/NH4I/β-mercaptoethanol at 60°C for 30 min. The obtained O-TMS derivative of VIL was detected by selected ion monitoring mode using the diagnostic ionsm/z223 and 252. Nandrolone was chosen as internal standard. The GC-MS method was fully validated by the following validation parameters: limit of detection (LOD) and quantitation (LOQ), linearity, precision, accuracy, specificity, stability, robustness, and ruggedness. LOD and LOQ were found to be 1.5 and 3.5 ng mL−1, respectively. The GC-MS method is linear in the range of 3.5–300 ng mL−1. The intra- and interday precision values were less than ≤3.62%. The intra- and interday accuracy values were found in the range of-0.26–2.06%. Finally, the GC-MS method was successfully applied to determine VIL in pharmaceutical formulation.

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