scholarly journals Management of validation of HPLC method for determination of acetylsalicylic acid impurities in a new pharmaceutical product

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Małgorzata Kowalska ◽  
Magdalena Woźniak ◽  
Michał Kijek ◽  
Paulina Mitrosz ◽  
Jerzy Szakiel ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Acetylsalicylic Acid ◽  
Hplc Method ◽  
Pharmaceutical Product ◽  
Forced Degradation ◽  
Limit Of Quantification ◽  
Constant Flow Rate ◽  
Technical Requirements ◽  
Repeatability And Reproducibility ◽  
Validation Tests

AbstractThe work mainly focused on a validation of the method for determining the content of salicylic acid and individual unknown impurities in new pharmaceutical product—tablets containing: 75, 100 or 150 mg of acetylsalicylic acid and glycine in the amount of 40 mg for each dosage. The separation of the components was carried out by means of HPLC, using a Waters Symmetry C18 column (4.6 × 250 mm, 5 μm) as the stationary phase. The mobile phase consisted of a mixture of 85% orthophosphoric acid, acetonitrile and purified water (2:400:600 V/V/V). Detection was carried out at a wavelength of 237 nm, with a constant flow rate of 1.0 ml min−1. In order to verify the method, linearity, precision (repeatability and reproducibility), accuracy, specificity, range, robustness, system precision, stability of the test and standard solution, limit of quantification and forced degradation were determined. Validation tests were performed in accordance with ICH (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use) guidelines. The method was validated successfully. It was confirmed that the method in a tested range of 0.005–0.40% salicylic acid with respect to acetylsalicylic acid content is linear, precise and accurate.

scholarly journals Development and Validation of an Analytical HPLC Method to Assess Chemical and Radiochemical Purity of [68Ga]Ga-NODAGA-Exendin-4 Produced by a Fully Automated Method

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 543
Author(s):  
Silvia Migliari ◽  
Antonino Sammartano ◽  
Marti Boss ◽  
Martin Gotthardt ◽  
Maura Scarlattei ◽  
...  
Keyword(s):  
Radiochemical Purity ◽  
Cell Mass ◽  
Hplc Method ◽  
European Medicines Agency ◽  
Guidance Document ◽  
Limit Of Quantification ◽  
Technical Requirements ◽  
Automated Method ◽  
Pet Tracer

Background: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in pancreatic islets, especially in β-cells, and highly expressed in human insulinomas and gastrinomas. In recent years several GLP-1R–avid radioligands have been developed to image insulin-secreting tumors or to provide a tentative quantitative in vivo biomarker of pancreatic β-cell mass. Exendin-4, a 39-amino acid peptide with high binding affinity to GLP-1R, has been labeled with Ga-68 for imaging with positron emission tomography (PET). Preparation conditions may influence the quality and in vivo behavior of tracers. Starting from a published synthesis and quality controls (QCs) procedure, we have developed and validated a new rapid and simple UV-Radio-HPLC method to test the chemical and radiochemical purity of [68Ga]Ga-NODAGA-exendin-4, to be used in the clinical routine. Methods: Ga-68 was obtained from a 68Ge/68Ga Generator (GalliaPharma®) and purified using a cationic-exchange cartridge on an automated synthesis module (Scintomics GRP®). NODAGA-exendin-4 contained in the reactor (10 µg) was reconstituted with HEPES and ascorbic acid. The reaction mixture was incubated at 100 °C. The product was purified through HLB cartridge, diluted, and sterilized. To validate the proposed UV-Radio-HPLC method, a stepwise approach was used, as defined in the guidance document released by the International Conference on Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH), adopted by the European Medicines Agency (CMP/ICH/381/95 2014). The assessed parameters are specificity, linearity, precision (repeatability), accuracy, and limit of quantification. Therefore, a range of concentrations of Ga-NODAGA-exendin-4, NODAGA-exendin-4 (5, 4, 3.125, 1.25, 1, and 0.75 μg/mL) and [68Ga]Ga-NODAGA-exendin-4 were analyzed. To validate the entire production process, three consecutive batches of [68Ga]Ga-NODAGA-exendin-4 were tested. Results: Excellent linearity was found between 5–0.75 μg/mL for both the analytes (NODAGA-exendin-4 and 68Ga-NODAGA-exendin-4), with a correlation coefficient (R2) for calibration curves equal to 0.999, average coefficients of variation (CV%) <2% (0.45% and 0.39%) and average per cent deviation value of bias from 100%, of 0.06% and 0.04%, respectively. The calibration curve for the determination of [68Ga]Ga-NODAGA-exendin-4 was linear with a R2 of 0.993 and CV% <2% (1.97%), in accordance to acceptance criteria. The intra-day and inter-day precision of our method was statistically confirmed using 10 μg of peptide. The mean radiochemical yield was 45 ± 2.4% in all the three validation batches of [68Ga]Ga-NODAGA-exendin-4. The radiochemical purity of [68Ga]Ga-NODAGA-exendin-4 was >95% (97.05%, 95.75% and 96.15%) in all the three batches. Conclusions: The developed UV-Radio-HPLC method to assess the radiochemical and chemical purity of [68Ga]Ga-NODAGA-exendin-4 is rapid, accurate and reproducible like its fully automated production. It allows the routine use of this PET tracer as a diagnostic tool for PET imaging of GLP-1R expression in vivo, ensuring patient safety.

Transfer of Low Dose Aspirin Into Human Milk

2017 ◽  
Vol 33 (2) ◽  
pp. 296-299 ◽  
Author(s):  
Palika Datta ◽  
Kathleen Rewers-Felkins ◽  
Raja Reddy Kallem ◽  
Teresa Baker ◽  
Thomas W. Hale
Keyword(s):  
Salicylic Acid ◽  
Human Milk ◽  
Acetylsalicylic Acid ◽  
Low Dose ◽  
Average Concentration ◽  
Limit Of Quantification ◽  
Milk Samples ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Infant Dose

Background: Aspirin has antipyretic and anti-inflammatory properties and is frequently used by pregnant and lactating women. However, its transfer in human milk when administered at low dose has not been reported. Research aim: This study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite, salicylic acid, into human milk following the use of low dose aspirin. Methods: In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours from seven breastfeeding women after a steady-state daily dose of 81 mg of aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined by liquid chromatography–tandem mass spectrometry. Results: Acetylsalicylic acid levels were below the limit of quantification (0.61 ng/ml) in all the milk samples, whereas salicylic acid was detected at very low concentrations. The average concentration of salicylic acid observed was 24 ng/ml and the estimated relative infant dose was 0.4%. Conclusion: Acetylsalicylic acid transfer into milk is so low that it is undetectable even by highly sophisticated methodology. Salicylic acid does appear in the human milk in comparatively low amounts, which are probably subclinical in infants. Thus, the daily use of an 81-mg dose of aspirin should be considered safe during lactation.

A new simple RP-HPLC Method development, Validation and Forced degradation studies of Bilastine

2021 ◽  
pp. 183-187
Author(s):  
Khushbu K. Patel ◽  
Arati M. Patel ◽  
C. N. Patel
Keyword(s):  
Retention Time ◽  
Dosage Form ◽  
Method Development ◽  
Limit Of Detection ◽  
Hplc Method ◽  
Forced Degradation ◽  
Limit Of Quantification ◽  
Pharmaceutical Dosage Form ◽  
Ich Guidelines ◽  
Hplc Method Development

A new simple, rapid, accurate and precise method for estimation of Bilastine in pharmaceutical dosage form by reverse phase liquid chromatography. The developed method employed mobile phase was Acetonitrile and Ammonium acetate pH 5.0 adjusted with glacial acetic acid with 85:15% v/v and flow rate 1.0ml/min. Method was developed using column C18 Water (150 × 4.6mm, 5µm) and detection wavelength was 215nm. The retention time was found to be 2.519 min. the proposed method was successfully applied to the determination of Bilastine in dosage form. High linearity of developed method was confirmed over concentration range of 25- 150 µg/ml and co-relation co-efficient is 0.996. The percentage RSD for precision and accuracy of the method was found to be less than 2%. The recovery was in the range of 99 – 102% and limit of detection was found to be 0.45µg/ml and limit of quantification was found to be 1.20µg/ml. Bilastine was found to degrade under acid and oxidation conditions. There was no interference of excipient and degradation product in retention time so method was specific. Analytical parameter such as precision, accuracy, limit of detection, limit of quantification and robustness were determined according to international Conference on Harmonization (ICH) guidelines.

scholarly journals Analytical Method Development and Validation and Forced Degradation Stability-Indicating Studies of Favipiravir by RP-HPLC and UV in Bulk and Pharmaceutical Dosage Form

2021 ◽  
pp. 254-271
Author(s):  
Sayyed Nazifa Sabir Ali ◽  
Lajporiya Mobina ◽  
Manjra Mehfuza ◽  
Patel Seema ◽  
Aejaz Ahmed ◽  
...  
Keyword(s):  
Dosage Form ◽  
Method Development ◽  
Limit Of Detection ◽  
Hplc Method ◽  
Forced Degradation ◽  
Limit Of Quantification ◽  
Pharmaceutical Dosage Form ◽  
Rp Hplc ◽  
Method Development And Validation ◽  
Development And Validation

Aims: To develop and validate a new, simple, rapid, precise, and accurate An Eco-friendly RP-HPLC and UV-Method Development and Validation for an estimation of Favipiravir in Bulk and pharmaceutical dosage form followed by Forced Degradation Studies. Study Design: This was employed for UV-visible (200-400 nm and 400-800 nm respectively) and RP-HPLC method development using C 18 inertsil column and optimization of variables for Favipiravir estimation in bulk and formulations. Place and Duration of the Study: The present work was carried out at Ali-allana College of Pharmacy, Akkalkuwa between the duration of November-2020 to February-2021. Methodology: UV-Spectroscopic method was developed for the estimation of Favipiravir in the bulk and pharmaceutical dosage form. The solvent selected for the Favipiravir UV analysis was water, the solution in a range of 2-10µg/ml was scanned in the UV region from 200-400 nm and the λmax value was determined. The RP-HPLC method was developed on inertsil ODS-3V C18 150 mm x 4.6mm x 5μ column using buffer pH 3.5: acetonitrile [90:10] as mobile phase at flow rate 1.0 ml/min and PDA detection at 358 nm. Results: The maximum absorbance was observed at 358 nm. The wavelength 358 nm was selected for further analysis of Favipiravir. The calibration curve was determined using drug concentrations ranging from 2-10 µg/ml. The % recovery for accuracy was 100.50-100.76%. The method was to be precise with a % RSD value 0.51-1.37 and 0.77-1.78 for intraday and Interday respectively. The limit of detection (LOD) and limit of quantification (LOQ) was found to be 0.0723 &0.219 µg/ml respectively by UV method. The RP-HPLC method was shown to be linear in the 50-250 μg/ml concentration range. The limit of detection (LOD) and limit of quantification (LOQ) was found to be 2.186 & 6.626 μg/ml respectively. The method was to be precise with a % RSD value 0.25-1.53 and 0.86-1.68 for intraday and inter-day respectively. Conclusion: Here we conclude that the developed UV and RP-HPLC methods are precise, accurate, sensitive, and reproducible for the quantitative estimation of Favipiravir bulk and its formulation. The developed method can be used by the pharmaceutical industries for the routine analysis of Favipiravir, in particular by UV and RP-HPLC. The main features of the proposed method are economic and eco-friendly with less retention time around 5.0 min.

scholarly journals Dual Wavelength RP-HPLC Method for Simultaneous Determination of Two Antispasmodic Drugs: An Application in Pharmaceutical and Human Serum

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Najmul Hasan ◽  
Mathurot Chaiharn ◽  
Sauleha Khan ◽  
Hira Khalid ◽  
Nawab Sher ◽  
...  
Keyword(s):  
Simultaneous Determination ◽  
Limit Of Detection ◽  
Hplc Method ◽  
Stress Conditions ◽  
Dual Wavelength ◽  
Forced Degradation ◽  
Limit Of Quantification ◽  
Stability Indicating ◽  
Physiological Fluid

A reverse phase stability indicating HPLC method for simultaneous determination of two antispasmodic drugs in pharmaceutical parenteral dosage forms (injectable) and in serum has been developed and validated. Mobile phase ingredients consist of Acetonitrile : buffer : sulfuric acid 0.1 M (50 : 50 : 0.3 v/v/v), at flow rate 1.0 mL/min using a HibarμBondapak ODS C18column monitored at dual wavelength of 266 nm and 205 nm for phloroglucinol and trimethylphloroglucinol, respectively. The drugs were subjected to stress conditions of hydrolysis (oxidation, base, acid, and thermal degradation). Oxidation degraded the molecule drastically while there was not so much significant effect of other stress conditions. The calibration curve was linear with a correlation coefficient of 0.9999 and 0.9992 for PG and TMP, respectively. The drug recoveries fall in the range of 98.56% and 101.24% with 10 pg/mL and 33 pg/mL limit of detection and limit of quantification for both phloroglucinol and trimethylphloroglucinol. The method was validated in accordance with ICH guidelines and was applied successfully to quantify the amount of trimethylphloroglucinol and phloroglucinol in bulk, injectable form and physiological fluid. Forced degradation studies proved the stability indicating abilities of the method.

scholarly journals DETERMINATION OF MEFENAMIC ACID IN A TOPICAL EMULGEL BY A VALIDATED HPLC METHOD

2019 ◽  
pp. 86-90
Author(s):  
APICHART ATIPAIRIN ◽  
SOMCHAI SAWATDEE
Keyword(s):  
Mefenamic Acid ◽  
High Performance ◽  
Limit Of Detection ◽  
Degradation Products ◽  
Hplc Method ◽  
Gelling Agent ◽  
Forced Degradation ◽  
Limit Of Quantification ◽  
Intermediate Precision

Objective: The present study is aimed to develop and validate a simple, precise and accurate high-performance liquid chromatography (HPLC) method, according to ASEAN guideline for the validation of the analytical procedure, for the determination of mefenamic acid in a topical emulgel preparation. Methods: An emulgel of 1 % mefenamic acid was prepared using carbopol 940 as a gelling agent and cremophor EL as an emulsifying agent. It was diluted with ethanol to make a sample concentration of 200 mg/ml. The method used a C18 column (5 µm; 250 x 4.6 mm) with the mobile phase, consisting of acetonitrile, acetic acid, and water in a ratio of 75:1:24. The column was maintained at 25 °C. The flow rate was 1 ml/min and the injection volume was 10 ml. The peak response was monitored by UV at 282 nm. It was validated for specificity, range, linearity, precision, accuracy, limit of detection (LOD) and limit of quantification (LOQ). In addition, forced degradation (hydrolysis, oxidation and dry heat) was performed to determine the capability of the proposed method to analyze the chemical stability of the drug samples during storage. Results: The method was specific to the drug while other excipients did not interfere with the quantitation of mefenamic acid. It was linear in the concentration range of 1.29 to 806 mg/ml. LOD and LOQ were 4.88 and 14.78 mg/ml, respectively. Accuracy of the method was demonstrated by recovery experiments on the synthetic mixture method and the mean percent recovery was 101.10±1.56. Repeatability and intermediate precision were rugged with %RSD values of 1.30 and 1.07, respectively. The method could separate mefenamic acid from other degradation products of forced degradation. Conclusion: The HPLC method presented herein is simple, accurate, sensitive and reproducible for the determination of mefenamic acid in an emulgel. It is served as a stability-indicating method and can be used for the analysis of the drug during product development and stability studies.

scholarly journals Simultaneous Determination of Paracetamol, Acetyl Salicylic Acid, Mefenamic Acid and Cetirizine Dihydrochloride in the Pharmaceutical Dosage Form

2010 ◽  
Vol 7 (s1) ◽  
pp. S495-S503 ◽  
Author(s):  
Freddy H. Havaldar ◽  
Dharmendra L. Vairal
Keyword(s):  
Salicylic Acid ◽  
Mefenamic Acid ◽  
Dosage Form ◽  
Pharmaceutical Formulations ◽  
Reversed Phase ◽  
Hplc Method ◽  
Acetyl Salicylic Acid ◽  
Pharmaceutical Dosage Form ◽  
Constant Flow Rate

A simple, specific, accurate and economical isocratic reversed phase liquid chromatographic (RP-HPLC) method was developed and subsequently validated for the determination of paracetamol, acetyl salicylic acid, mefenamic acid and cetirizine dihydrochloride. Separation was achieved with a Nucleodur 100 C–18 column having 250 × 4.6 mm i.d. with 5 µm particle size and disodium hydrogen phosphate buffer adjusted to pH 6.5 using diluted orthophosphoric acid and acetonitrile (60:40 v∕v) as eluent at a constant flow rate of 1.0 mL per min. UV detection was performed at 220 nm. The retention time of acetyl salicylic acid, paracetamol, mefenamic acid and cetirizine dihydrochloride were 2.01 min, 2.92 min, 4.91 min and 10.2 min respectively. This method is simple, rapid and selective and can be used for routine analysis of analgesic and antipyretic drugs in pharmaceutical formulations. The proposed method was validated and successfully used for estimation of paracetamol, acetyl salicylic acid, mefenamic acid and cetirizine dihydrochloride in the pharmaceutical dosage form.

DEVELOPMENT AND VALIDATION OF STABILITY INDICATING RP-HPLC METHOD FOR AMISULPRIDE IN BULK AND PHARMACEUTICAL FORMULATION

INDIAN DRUGS ◽  
2012 ◽  
Vol 49 (04) ◽  
pp. 43-50
Author(s):  
K. M. L Manoja ◽  
◽  
B. M. Gurupadayya ◽  
S Srujana ◽  
L. V. Raaga ◽  
...  
Keyword(s):  
High Performance ◽  
Limit Of Detection ◽  
Internal Standard ◽  
Pharmaceutical Formulations ◽  
High Performance Liquid Chromatographic ◽  
Hplc Method ◽  
Pharmaceutical Formulation ◽  
Forced Degradation ◽  
Uv Detector ◽  
Limit Of Quantification

A simple, sensitive, rapid, robust and reproducible method for the determination of amisulpride using paracetamol as internal standard (IS) in bulk and pharmaceutical formulation was developed using reverse phase high performance liquid chromatographic method. The analysis was performed on C18 (250 4.6 mm, 5 mcm) column with a mobile phase consisting of 0.03 M potassium dihydrogen ortho phosphate buffer (pH 6.5), acetonitrile in the ratio of 67:33 (V/V) with a flow rate of 1 mL/min. The analyte was monitored with UV detector at 263 nm. In the developed method amisulpride elutes at retention time of 4.4 min and paracetamol (IS) at 3.3 min. The proposed method is having linearity in the concentration range from 10-100 mcg/mL of amisulpride. The method was validated with respect to system suitability, linearity, precision, limit of detection (LOD) and limit of quantification (LOQ), accuracy (recovery),ruggedness, robustness, stability, forced degradation studies (specificity). The proposed method can be readily utilized for bulk drug and pharmaceutical formulations of amisulpride.

scholarly journals A validated stability indicating RP-HPLC method for the quantification of Canagliflozin

2018 ◽  
Vol 9 (1) ◽  
pp. 206
Author(s):  
Sreenivasulu S ◽  
Rameswara Rao M ◽  
Chandra Sekhar KB
Keyword(s):  
High Performance ◽  
Limit Of Detection ◽  
Pharmaceutical Formulations ◽  
High Performance Liquid Chromatographic ◽  
Hplc Method ◽  
Plate Count ◽  
Forced Degradation ◽  
Chromatographic Study ◽  
Limit Of Quantification ◽  
Stability Indicating

A simple, authentic and stability indicating high performance liquid chromatographic method for determination of Canagliflozin in bulk and pharmaceutical formulations was developed and validated as per ICH Q2 R1 Guidelines, A C18 Column (250mm length×4.6 mm diameter x 5 μm particle size) with a mobile phase consisting of Acetonitrile: 1-octanesulphonic acid in a ratio of 70:30 v/v was employed for the chromatographic study. A flow rate of 1.0 mL/min with an injection volume of 20 μL was selected for this study and the proposed method was validated with different parameters such as Linearity, Precision, Accuracy, Robustness, Ruggedness, Limit of Detection (LOD) and Limit of Quantification (LOQ). Canagliflozin was eluted at 3.4 ± 0.5 min and detected at 245 nm. The method is linear over the concentration range of 10-100 μg/mL with correlation co-efficient r = 0.9997. The plate count and tailing factor was found 5398 and 1.05 respectively. The LOD and LOQ were found to be 0.0170 μg/mL and 0.1705 μg/mL respectively. The percentage recovery was achieved in the range of 98-102%, which was within the acceptance criteria. Developed method was employed to determine the amount of Canagliflozinpresent in dosage form (Sulisent). The stabilityof the method was demonstrated by forced degradation studies of drug in which it was degraded under conditions of hydrolysis (acidic and alkaline), oxidation, photolytic and thermal stress as per ICH guideline Q1A (R2).

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