scholarly journals Development and Validation of 2-Azaspiro [4,5] Decan-3-One (Impurity A) in Gabapentin Determination Method Using qNMR Spectroscopy

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1656
Author(s):  
Nataliya E. Kuz’mina ◽  
Sergey V. Moiseev ◽  
Mikhail D. Khorolskiy ◽  
Anna I. Lutceva
Keyword(s):  
Test Procedure ◽  
Active Pharmaceutical Ingredient ◽  
Test Methods ◽  
Intermediate Precision ◽  
Coefficients Of Variation ◽  
Validation Parameters ◽  
Limit Of Quantitation ◽  
Student’S T ◽  
Development And Validation ◽  
Student’S T Test

The authors developed a 1H qNMR test procedure for identification and quantification of impurity A present in gabapentin active pharmaceutical ingredient (API) and gabapentin products. The validation studies helped to determine the limit of quantitation and assess linearity, accuracy, repeatability, intermediate precision, specificity, and robustness of the procedure. Spike-and-recovery assays were used to calculate standard deviations, coefficients of variation, confidence intervals, bias, Fisher’s F test, and Student’s t-test for assay results. The obtained statistical values satisfy the acceptance criteria for the validation parameters. The authors compared the results of impurity A quantification in gabapentin APIs and capsules by using the 1H qNMR and HPLC test methods.

scholarly journals Reversed phase HPLC for strontium ranelate: Method development and validation applying experimental design

2018 ◽  
Vol 68 (2) ◽  
pp. 171-183
Author(s):  
Béla Kovács ◽  
Lajos Kristóf Kántor ◽  
Mircea Dumitru Croitoru ◽  
Éva Katalin Kelemen ◽  
Mona Obreja ◽  
...  
Keyword(s):  
Experimental Design ◽  
Strontium Ranelate ◽  
Method Development ◽  
Limit Of Detection ◽  
Cost Effective ◽  
Reversed Phase ◽  
Hplc Method ◽  
Intermediate Precision ◽  
Limit Of Quantitation ◽  
Development And Validation

Abstract A reverse-phase HPLC (RP-HPLC) method was developed for strontium ranelate using a full factorial, screening experimental design. The analytical procedure was validated according to international guidelines for linearity, selectivity, sensitivity, accuracy and precision. A separate experimental design was used to demonstrate the robustness of the method. Strontium ranelate was eluted at 4.4 minutes and showed no interference with the excipients used in the formulation, at 321 nm. The method is linear in the range of 20–320 μg mL−1 (R2 = 0.99998). Recovery, tested in the range of 40–120 μg mL−1, was found to be 96.1–102.1 %. Intra-day and intermediate precision RSDs ranged from 1.0–1.4 and 1.2–1.4 %, resp. The limit of detection and limit of quantitation were 0.06 and 0.20 μg mL−1, resp. The proposed technique is fast, cost-effective, reliable and reproducible, and is proposed for the routine analysis of strontium ranelate.

scholarly journals Validation of analytical method for determination of furosemide in extemporaneous syrup

2017 ◽  
Author(s):  
D. Alfred-Ugbenbo ◽  
O. A. Zdoryk ◽  
V. A. Georgiyants
Keyword(s):  
Sodium Hydroxide Solution ◽  
Correlation Coefficients ◽  
Active Pharmaceutical Ingredient ◽  
Stability Study ◽  
Assay Method ◽  
Pure Substance ◽  
Ultraviolet Region ◽  
Validation Parameters ◽  
Development And Validation ◽  
Medicinal Drugs

Introduction. Extreme syrups can be manufactured using substances or ready medicinal drugs as the active pharmaceutical ingredient. There is a necessity in the development and validation of analytical methods that can be used for quality control of pharmaceutical manufacturing of syrups containing furosemide.The aim of the study – to develop and validate assay method for furosemide in extemporaneous syrups prepared from both pure substance and finished products. Methods of the research. For proposed UV spectrophotometric assay method the conditions of analysis, sample preparation and validation characteristics were defined. Suspensions of substance and crushed commercial tablets were dissolved in 0.1 M sodium hydroxide solution and evaluated spectrophotometrically in ultraviolet region of light at a wavelength 271 nm using method of specific absorbance.Results and Discussion. Samples comply with the Beer-Lambert Bouguer law within the concentration range of 8×10-3 – 1.2×10-2 mg/ml with correlation coefficients ≥ 0.9981. The uncertainty of the methods was well within the critical value of the error (0.72 %≤ maxΔAs) for both samples of syrup containing pure substance and commercial tablets. Recovery studies for furosemide in syrup samples of substance and crushed commercial tablets yielded 99.92 ±0.54 % and 99.14±0.16 % respectively. Assay limit of ±10 % by the validation parameters: specificity, linearity, precision, accuracy within the range of 80–120 % of the nominal contents was met by all compounded preparations.Conclusions. The results of validation proved that this method can be reproduced correctly and is suitable for use in pharmaceutical analysis. Adoption of this method is planned in evaluating uniformity of content and, in combination of other methods, ascertain chemical stability study of compounded furosemide syrups.

scholarly journals Development and Validation of an Automated Step Ergometer

2014 ◽  
Vol 43 (1) ◽  
pp. 113-124
Author(s):  
Maria do Socorro C. de Sousa ◽  
Rodrigo R. Aniceto ◽  
Gabriel R. Neto ◽  
Ravi C. T. de Araújo ◽  
Juliana B. C. de Sousa ◽  
...  
Keyword(s):  
Cardiorespiratory Fitness ◽  
Development Process ◽  
Gas Analysis ◽  
Training Condition ◽  
Step Test ◽  
The Subject ◽  
Student’S T ◽  
Development And Validation ◽  
And Training ◽  
Student’S T Test

Abstract Laboratory ergometers have high costs, becoming inaccessible for most of the population, hence, it is imperative to develop affordable devices making evaluations like cardiorespiratory fitness feasible and easier. The objective of this study was to develop and validate an Automated Step Ergometer (ASE), adjusted according to the height of the subject, for predicting VO2max through a progressive test. The development process was comprised by three steps, the theoretical part, the prototype assembly and further validation. The ASE consists in an elevating platform that makes the step at a higher or lower level as required for testing. The ASE validation was obtained by comparing the values of predicted VO2max (equation) and direct gas analysis on the prototype and on a, treadmill. For the validation process 167 subjects with average age of 31.24 ± 14.38 years, of both genders and different degrees of cardiorespiratory fitness, were randomized and divided by gender and training condition, into untrained (n=106), active (n=24) and trained (n=37) subjects. Each participant performed a progressive test on which the ASE started at the same height (20 cm) for all. Then, according to the subject’s height, it varied to a maximum of 45 cm. Time in each stage and rhythm was chosen in accordance with training condition from lowest to highest (60-180 s; 116-160 bpm, respectively). Data was compared with the student’s t test and ANOVA; correlations were tested with Pearson’s r. The value of α was set at 0.05. No differences were found between the predicted VO2max and the direct gas analysis VO2max, nor between the ASE and treadmill VO2max (p= 0.365) with high correlation between ergometers (r= 0.974). The values for repeatability, reproducibility, and reliability of male and female groups measures were, respectively, 4.08 and 5.02; 0.50 and 1.11; 4.11 and 5.15. The values of internal consistency (Cronbach’s alpha) among measures were all >0.90. It was verified that the ASE prototype was appropriate for a step test, provided valid measures of VO2max and could therefore, be used as an ergometer to measure cardiorespiratory fitness.

Determination of Selected Opiates in Hair Samples Using Microextraction by Packed Sorbent: A New Approach for Sample Clean-up

2019 ◽  
Vol 43 (6) ◽  
pp. 465-476 ◽  
Author(s):  
Tiago Rosado ◽  
Mário Barroso ◽  
Duarte Nuno Vieira ◽  
Eugenia Gallardo
Keyword(s):  
Formic Acid ◽  
Ammonium Hydroxide ◽  
New Approach ◽  
Microextraction By Packed Sorbent ◽  
Coefficients Of Variation ◽  
Hair Samples ◽  
Limit Of Quantitation ◽  
Relative Errors ◽  
Packed Sorbent ◽  
Development And Validation

Abstract In this article the development and validation of an analytical method using microextraction by packed sorbent (MEPS) to determine tramadol (TRM), codeine (COD), morphine (MOR), 6-acetylcodeine (6-AC), 6-monoacetylmorphine (6-MAM) and fentanyl (FNT) in hair samples by gas chromatography coupled to tandem mass spectrometry (GC–MS-MS) is presented. The MEPS used a mixed mode sorbent, and the steps for sample cleanup were conditioning (three cycles of 250 μL of methanol and three cycles of 250 μL formic acid 2%); sample load (15 cycles of 150 μL); wash (150 μL of 3.36% formic acid); and elution (eight cycles of 100 μL of ammonium hydroxide 2.36% (in methanol)). Linearity was obtained from the lower limit of quantitation (LLOQ) up to 5 ng/mg, with all target compounds revealing determination coefficients >0.99. The LLOQs achieved were 0.01 ng/mg for TRM, COD and 6-AC, and 0.025 ng/mg for MOR, 6-MAM and FNT. The recoveries ranged from 74 to 90% (TRM), 51 to 59% (COD), 22 to 36% (MOR), 69 to 99% (6-AC), 53 to 61% (6-MAM) and 75 to 86% (FNT). Precision and accuracy revealed coefficients of variation typically below 15% and relative errors within a ±15% interval, respectively. This new approach has proven to be an excellent alternative to classic procedures, reducing the volumes of organic solvents required.

scholarly journals Development and Validation of Estimation of Genotoxic Impurity (Triethyl orthoformate content) in 5-methyl-4-isoxazole carboxylic acid (5-MIA) by using GC Technique

2021 ◽  
Vol 37 (2) ◽  
pp. 348-353
Author(s):  
Mohan bhatale ◽  
Neelakandan kaliyaperumal ◽  
Gopalakrishnan Mannathusamy ◽  
Gurunathan ramalingam
Keyword(s):  
Method Development ◽  
Limit Of Detection ◽  
Fused Silica ◽  
Triethyl Orthoformate ◽  
Concentration Limit ◽  
Simultaneous Estimation ◽  
Validation Parameters ◽  
Limit Of Quantitation ◽  
Gas Chromatographic Method ◽  
Development And Validation

A simple, selective, precise and accurate Gas chromatographic method for determination of Triethyl orthoformate content (Genotoxic impurity) in 5-MIA is reported. The GC method development and validation as per the International Council for Harmonisation (ICH) guidelines Q2(R1). The effective chromatographic separations were achieved on DB-624, 60 m × 0.53 mm ID, with film thickness of 3.0 μm (Fused silica capillary column), Capillary injector temperature of 150°C, and Nitrogen Carrier gas. This method is unique as there is no UV response; hence GC Method was developed for Triethyl orthoformate. The elution was accomplished with the flow rate of 5.0 mL/min and Split Flow of 10 mL/minute. Detection was performed with FID detector (temp. 260°C) and with column oven temperature program. Methods range from limit of quantitation (LOQ) to 150% level with respect to specification concentration limit of impurity is linear and correlation coefficient of impurity is > 0.99. The linearity of Triethyl orthoformate covered from LOQ to 113 ppm (ie. LOQ to 150% of specification limit) and LOQ to 19 ppm wrt standard concentration. The limit of detection (LOD)values were observed were 2.5 ppm and limit of quantitation (LOQ) were 7.7 ppm, respectively. The parameters selected for the method validated were from international conference on harmonization guidelines, Indian pharmacopeia, USP. The percentage recovery from LOQ, 50% ,100% to 150% level of content were 87.70%, 98.60%, 102.25 and 96.59% respectively. The %RSD values were for LOQ to 150% were from 1.64%, 0.89%, 1.78 % and 1.49%. The range was covered from LOQ to 150% of standard concentration. The results of validation parameters were found in the acceptance range. Standard and sample were stable up to 30 h at when stored at room temperature. Also it was quite robust for the small change in method parameter like, change in column oven temperature(± 5 degree). Hence from the above parameter it was concluded that the GC method with FID detector is selective, precise, linear, and robust for simultaneous estimation of Triethyl orthoformate in Drug Substances.

scholarly journals Development and validation of gas chromatography methods for the control of volatile impurities in the pharmaceutical substance dutasteride

2016 ◽  
Author(s):  
Aleksandra Groman ◽  
Elżbieta U. Stolarczyk ◽  
Marta Jatczak ◽  
Elżbieta Lipiec-Abramska
Keyword(s):  
Gas Chromatography ◽  
Carbon Tetrachloride ◽  
Direct Injection ◽  
Test Procedure ◽  
Active Pharmaceutical Ingredient ◽  
Experimental Conditions ◽  
Limit Test ◽  
Development And Validation ◽  
Optimization Of Experimental Conditions ◽  
Volatile Impurities

Dutasteride, N-[2,5-Bis(trifluoromethyl)phenyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide, is an active pharmaceutical ingredient (API) which inhibits the conversion of testosterone to dihydrotestosterone. Dutasteride as a 5-reductase inhibitor is useful for the treatment of benign prostatic hyperplasia (BPH) and prostate cancer. Because of a large variety of solvents and reagents used in the synthesis, it was necessary to develop new, sensitive and selective gas chromatography (GC) methods. The optimization of the methods consisted in selecting different types of sample injection and detection as well as optimization of experimental conditions that allowed to meet the appropriate range (10-120% of the specification limit) and suitable detection limits (LOD) of compounds. Significant differences in the volatility of these compounds forced the division into volatile solvents (methanol, acetonitrile, dichloromethane, ethyl acetate, heptane and toluene) analyzed with the use of the gas chromatography with headspace (GC-HS) and less volatile compounds (pyridine, dimethylformamide, 1,4-dioxane, acetic acid, ethylene glycol, 4-dimethylaminopyridine) analyzed with the use of gas chromatography with direct injection (GC-FID). Benzene, carbon tetrachloride and 1,2-dichloroethane are potential contaminants of toluene and dichloromethane, thus the control of these solvents was a limit test procedure. Due to the low specification limits for benzene (2 ppm), carbon tetrachloride (4 ppm) and 1,2-dichloroethane (5 ppm) it was neccesery to use gas chromatography with mass spectrometry detection (GC-MS). All three new methods were validated according to the requirements of the ICH (International Conference on Harmonization) validation guideline Q2R1 and the guideline for residual solvents Q3C. Specificity, precision, accuracy, linearity, limits of detection and quantitation and robustness were determined and the results meeting the acceptance criteria were obtained.

scholarly journals Development and Validation of RP–HPLC Method for Estimation of Curcumin from Nanocochleates and Its Application in in–vivo Pharmacokinetic Study

2020 ◽  
Vol 67 (4) ◽  
pp. 110-1110
Author(s):  
Sameer Nadaf ◽  
Suresh Killedar
Keyword(s):  
Rat Plasma ◽  
Hplc Method ◽  
Pharmacokinetic Parameters ◽  
Statistical Control ◽  
Rp Hplc ◽  
Relative Standard ◽  
Validation Parameters ◽  
Limit Of Quantitation ◽  
Development And Validation

A reliable RP-HPLC analytical method with UV detection at 421 nm was developed and validated for the quantitative determination of curcumin from rat plasma after oral administration of curcumin loaded nanocochleates (CU-NC) to rats. The chromatographic separation was performed on HIQ SIL, C18 (250 mm × 4.6 mm) column using methanol and water (80:20 v/v) as mobile phase, at 1.0 mL/min flow rate. Validation parameters included linearity, accuracy, precision, and limit of quantitation and detection. Good linearity was obtained over the range of 2.5–100 μg/mL (R2 = 0.9979) of curcumin. The developed HPLC method was precise, with <2% relative standard deviation. Accuracy, stability, and robustness studies were also found to be acceptable. Bland-Altman plot showed an acceptable repeatability coefficient. The method was under statistical control, revealed by a control chart. After CU–NC administration, pharmacokinetic parameters i.e. Cmax, AUC0-∞, and AUMC0-∞, were observed to be 97.69 ± 10.84 μg/mL, 1402.77 ± 9.67 (μg/mL) ∙ h, and 35140.16 ± 14.67 (μg/mL) ∙ h2, respectively. This simple and precise method can be effectively implemented for routine analysis.

scholarly journals VALIDATED STABILITY-INDICATING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR THE ESTIMATION OF TORSEMIDE

2019 ◽  
pp. 26-32
Author(s):  
LALITHA KV ◽  
RAVEENDRA REDDY J ◽  
DEVANNA N
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
High Performance ◽  
Limit Of Detection ◽  
Active Pharmaceutical Ingredient ◽  
Chromatography Method ◽  
Relative Standard ◽  
Validation Parameters ◽  
Limit Of Quantitation ◽  
Hplc Technique

Objective: This assessment depicts the strength of exhibiting reverse-phase high performance liquid chromatography (RP-HPLC) method for the estimation of torsemide in pharmaceutical estimation structures. Methods: In the present work, total protein-HPLC technique has been produced for the estimation of torsemide active pharmaceutical ingredient (API). Constrained degradation HPLC strategy was created with versatile mobile phase of methanol:water in the proportion of 90:10 v/v. The stream pace of 1 ml/min was utilized on Inertsil ODS 3V segment (250 mm×4.6 mm, 5 μm molecule size). Results: The retention time of torsemide was seen at 8.267 min, method was validated for all validation parameters as per the International Council for Harmonization guidelines. The linearity range was 10–60 μg/ml, correlation coefficient was 0.9993, and percentage relative standard deviation in the precision studies was <2%, with percentage recovery 100.56–101.03 (within acceptable range of 98–102%). The assay result was found to be 100.88% (i.e., within 95–105%), passes the specifications for robustness parameters. Limit of detection of torsemide was found to be 0.0162 μg/ml and limit of quantitation of torsemide was found to be 0.0534 μg/ml. Conclusion: The medication was exceptionally delicate to antacid pursued by at risk to corrosive, photolytic, warm, and oxidative conditions. The created and approved method showing HPLC technique is observed to be direct, exact, precise, explicit, and powerful. Henceforth, the technique can be utilized routinely for the estimation of torsemide API.

Development and Validation of Head-space Gas Chromatographic Method in Tandem with Flame ionized detection for the determination of Residual solvents in Simeprevir API Synthesis

2021 ◽  
pp. 5175-5181
Author(s):  
C. Hazarathaiah Yadav ◽  
A. Malli Babu
Keyword(s):  
Limit Of Detection ◽  
Intermediate Precision ◽  
Residual Solvent ◽  
Residual Solvents ◽  
Flame Ionization ◽  
Limit Of Quantitation ◽  
Reference Material Certification ◽  
Precision System ◽  
Gas Chromatographic Method ◽  
Development And Validation

Residual solvent testing is an integral part of reference material certification. A gas chromatography/flame ionization detector/headspace method has been developed and validated to detect and quantitate commonly used residual solvents in our production processes: Methanol, Tetrahydrofuran, Toluene, Dichloromethane and Dichloroethane in Simeprevir API. A simple and selective HS-GC method is described for the determination & quantification of Residual Solvents in Simeprevir API. Chromatographic separation was achieved on USP G43 equivalent capillary column Thermo Scientific™ Trace GOLD™ TG-624 SilMS, 30m × 0.32mm × 1.8µm column (P/N 26059-3390) using nitrogen as carrier gas by using different temperature gradient of FID Detectors. Linearity was observed in the range 40-120% of standard concentrations for Methanol, Tetrahydrofuran, Toluene, Dichloromethane and Dichloroethane (r2>0.999) for the amount of solvent estimated by the proposed methods was in good agreement. The proposed methods were validated. The accuracy of the methods was assessed by recovery studies at three different levels. Recovery experiments indicated the absence of interference from commonly encountered diluent and API. The method was found to be precise as indicated by the repeatability analysis, showing %RSD less than 10 for Methanol, Tetrahydrofuran, Toluene, Dichloromethane and Dichloroethane. All statistical data proves validity of the methods and can be used for routine analysis of pharmaceutical active ingredients for estimation of Residual Solvents of Methanol, Tetrahydrofuran, Toluene, Dichloromethane and Dichloroethane in Simeprevir. Baseline separation of all five solvents and Simeprevir API is achieved within 20.5 minutes of analysis time. Method validation comprised the following parameters: limit of detection (LOD), limit of quantitation (LOQ), linearity and range, accuracy, precision (repeatability and intermediate precision), system suitability, specificity, and robustness. Linearity and LOQ (ppm) are listed for each solvent in manuscript. The present method was proven to be robust and accurate for quantitative analysis of residual solvent in neat materials.

scholarly journals Measurement of HDO Products Using GC-TCD: Towards Obtaining Reliable Analytical Data

2018 ◽  
Vol 5 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Oman Zuas ◽  
Harry Budiman ◽  
Dieni Mansur ◽  
Muhammad Rizky Mulyana
Keyword(s):  
Method Development ◽  
Limit Of Detection ◽  
Analytical Data ◽  
Sample Treatment ◽  
Gaseous Products ◽  
Relative Standard ◽  
Validation Parameters ◽  
Limit Of Quantitation ◽  
Method Development And Validation ◽  
Development And Validation

Abstract This paper reported the method development and validation of a gas chromatography with thermal conductivity detector (GC-TCD) method for the measurement of the gaseous products of hydrodeoxygenation (HDO). The method validation parameters include selectivity, precision (repeatability and reproducibility), accuracy, linearity, limit of detection (LoD), limit of quantitation (LoQ), and robustness. The results showed that the developed method was able to separate the target components (H2, CO2, CH4 and CO) from their mixtures without any special sample treatment. The validated method was selective, precise, accurate, and robust. Application of the developed and validated GC-TCD method to the measurement of by-product components of HDO of bio-oil revealed a good performance with relative standard deviation (RSD) less than 1.0% for all target components, implying that the process of method development and validation provides a trustworthy way of obtaining reliable analytical data.

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