Establishment and Validation of an ICP-MS Method for Simultaneous Measurement of 24 Elemental Impurities in Ubenimex APIs According to USP/ICH guidelines

2020 ◽  
Vol 16 ◽  
Author(s):  
Ming-Juan Zhao ◽  
Lei Cheng ◽  
Yu-Jia Huang ◽  
Ying Tao ◽  
Xiao Gu ◽  
...  
Keyword(s):  
Correlation Coefficients ◽  
The United States ◽  
Pharmaceutical Products ◽  
Intermediate Precision ◽  
Elemental Impurities ◽  
Ich Guidelines ◽  
Icp Ms ◽  
Validation Procedure ◽  
Actual Target

Background: To control the potential presence of heavy metals in pharmaceuticals, the United States Pharmacopeia (USP) and International Conference on Harmonization (ICH) have put forth new requirements and guidelines. USP 232 and ICH Q3D specify 24 elemental impurities and their concentration limits in consideration of the permitted daily exposure (PDE) of different drug categories (oral, parenteral and inhalation). while USP 233 describes more information about sample preparation and method validation procedure. Objective: To establish and verify an ICP-MS method for the determination of 24 elemental impurities (Cd, Pb, As, Hg, Co, V, Ni, Tl, Au, Pd, Ir, Os, Ph, Ru, Se, Ag, Pt, Li, Sb, Ba, Mo, Cu, Sn, Cr) in ubenimex APIs according to USP/ICH guidelines. Method: Samples were analyzed by ICP-MS after direct dissolution in diluted acid solution. All elements were detected in He/HEHe mode (except for Li, which was in No gas mode). Results: The spiked recoveries were within 80-120% except Hg (79.4% at 0.5J level in HEHe mode) and Cd (121.9% at 0.5J level in HE mode). The RSD of repeatability (N = 6) for all elements were < 7.0% and intermediate precision (N = 12) were < 9.0%. The correlation coefficients of linear (R) for 24 elements were all > 0.998. The limits of detection (LOD) were < 1 ng/mL except that Ni was 1.23 ng/mL in HEHe mode. The contents of 24 elements in 3 batches of samples were significantly lower than the actual target limit of ICH, while the highest content of Pd did not exceed 10 μg/g. Conclusion: The established method was proved to be simple, sensitive and accurate. It successfully applied to the elemental impurity determination in 3 batches of ubenimex APIs from different manufactories. This method also provided technical guidance for determination of multiple elements in pharmaceutical products.

Development and Validation of an Eco-Friendly and Low-Cost Method for the Quantification of Cefepime Hydrochloride in Powder for Injectable Solution Using Infrared (IR) Spectroscopy

2020 ◽  
Vol 16 (4) ◽  
pp. 456-464
Author(s):  
Danilo F. Rodrigues ◽  
Hérida R.N. Salgado
Keyword(s):  
Ir Spectroscopy ◽  
Low Cost ◽  
Pharmaceutical Preparations ◽  
Potassium Bromide ◽  
Pharmaceutical Products ◽  
Injectable Formulation ◽  
Ich Guidelines ◽  
Lactam Ring ◽  
Development And Validation

Background: A simple, eco-friendly and low-cost Infrared (IR) method was developed and validated for the analysis of Cefepime Hydrochloride (CEF) in injectable formulation. Different from some other methods, which employ organic solvents in the analyses, this technique does not use these types of solvents, removing large impacts on the environment and risks to operators. Objective: This study aimed at developing and validating a green analytical method using IR spectroscopy for the determination of CEF in pharmaceutical preparations. Methods: The method was validated according to ICH guidelines and the quantification of CEF was performed in the spectral region absorbed at 1815-1745 cm-1 (stretching of the carbonyl group of β- lactam ring). Results: The validated method showed to be linear (r = 0.9999) in the range of 0.2 to 0.6 mg/pellet of potassium bromide, as well as for the parameters of selectivity, precision, accuracy, robustness and Limits of Detection (LOD) and Quantification (LOQ), being able to quantify the CEF in pharmaceutical preparations. The CEF content obtained by the IR method was 103.86%. Conclusion: Thus, the method developed may be an alternative in the quality control of CEF sample in lyophilized powder for injectable solution, as it presented important characteristics in the determination of the pharmaceutical products, with low analysis time and a decrease in the generation of toxic wastes to the environment.

scholarly journals Intra-Laboratory Validation of Alpha-Galactosidase Activity Measurement in Dietary Supplements

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1566
Author(s):  
Elena Fabris ◽  
Michela Bulfoni ◽  
Alessandro Nencioni ◽  
Emanuele Nencioni
Keyword(s):  
Dietary Supplements ◽  
Good Manufacturing Practice ◽  
Activity Measurement ◽  
Intermediate Precision ◽  
Method Performance ◽  
Intestinal Gas ◽  
Technical Requirements ◽  
Ich Guidelines ◽  
Alpha Galactosidase

Introduction: Alpha-galactosidase (α-Gal) is an enzyme responsible for the hydrolyzation of glycolipids and glycoprotein commonly found in dietary sources. More than 20% of the general population suffers from abdominal pain or discomfort caused by intestinal gas and by indigested or partially digested food residuals. Therefore, α-Gal is used in dietary supplements to reduce intestinal gases and help complex food digestion. Marketed enzyme-containing dietary supplements must be produced in accordance with the Food and Drug Administration (FDA) regulations for Current Good Manufacturing Practice (cGMPs). Aim: in this work we illustrated the process used to develop and validate a spectrophotometric enzymatic assay for α-Gal activity quantification in dietary supplements. Methods: The validation workflow included an initial statistical-phase optimization of materials, reagents, and conditions, and subsequently a comparative study with another fluorimetric assay. A final validation of method performance in terms of specificity, linearity, accuracy, intermediate-precision repeatability, and system precision was then executed. Results and conclusions: The proven method achieved good performance in the quantitative determination of α-Gal activity in commercial food supplements in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals (ICH) guidelines and is suitable as a rapid in-house quality control test.

SIMULTANEOUS ESTIMATION AND VALIDATION OF RAMIPRIL AND TELMISARTAN BY UV SPECTROPHOTOMETRY

INDIAN DRUGS ◽  
2014 ◽  
Vol 51 (09) ◽  
pp. 31-35
Author(s):  
R Rambabu ◽  
◽  
S Vidyadhara ◽  
J Subbarao
Keyword(s):  
Spectrophotometric Method ◽  
Correlation Coefficients ◽  
Simultaneous Equation ◽  
Dosage Forms ◽  
Simultaneous Estimation ◽  
Uv Spectrophotometry ◽  
Intermediate Precision ◽  
Pharmaceutical Dosage Forms ◽  
Sensitive Spectrophotometric Method

A simple and sensitive spectrophotometric method for the determination of ramipril and telmisartan in pharmaceutical dosage forms has been developed. The absorption maxima were found at 220nm for ramipril and 297nm for telmisartan using 0.1N NaOH as solvent. Beer’s law was obeyed for both the drugs in the concentration range of 2-10μg/ml with correlation coefficients 0.999 for both ramipril and telmisartan. The limits of detection for ramipril and telmisartan were found to be 0.142 and 0.405μg/mL respectively and the limits of quantitation were 0.43 and 1.22μg/mL. Accuracy of the method was verified by performing recovery studies using simultaneous equation method and found to be 98.33 to 99.54%w/w for ramipril and 99.36 to 99.82 %w/w for telmisartan. %RSD of repeatability and intermediate precision studies were found to be <2 for both the drugs. Ruggedness of the method was checked by changing analyst worked and instrument used. In both the cases, the %RSD was found to be less than 2.

Determination of elemental impurities of Arsenic, Cadmium, Mercury, Lead and Palladium content in Testosterone propionate by using ICP-MS

2021 ◽  
pp. 195-202
Author(s):  
Suresh P. ◽  
Konda Ravi Kumar
Keyword(s):  
Nitric Acid ◽  
Present Method ◽  
Testosterone Propionate ◽  
Rf Power ◽  
High Toxicity ◽  
Elemental Impurities ◽  
Icp Ms ◽  
Energy Discrimination ◽  
Palladium Content

The aim of the present work is to develop and establish a validated analytical method for the determination of arsenic, cadmium, mercury, lead and palladium content in testosterone propionate by using inductive coupled plasma mass spectroscopy (ICP-MS). Samples were analyzed after a preparation of sample solution by dissolving in suitable solvents of concentrated nitric acid and concentrated hydrochloric acid. In the present method, RF power of 1550 watts, RF matching is 1.80 V, nebulizer flow of 0.10 rps and plasma view at spectrum mode were used. Octopole conditions are He flow is on, He flow rate is 4.3 mL/min and energy discrimination is 3.0 V were used. Significant savings in sample volumes, reagents, analysis cost and time are realized. Arsenic, cadmium, mercury, lead and palladium are primary concerned due to their high toxicity and potential contaminants should be limited in testosterone propionate and the developed method was validated according to ICH and USP guidelines. The correlation coefficient, recovery rate, LOD and LOQ reached the acceptable limits. The validated method was selective, sensitive, rapid and capable of the determination of elemental impurities of arsenic, cadmium, mercury, lead and palladium content in bulk drugs.

scholarly journals Aniline Derived Bis-Schiff Base - Analytical Reagent for the Assay of Fe (III)

2018 ◽  
Vol 69 (11) ◽  
pp. 3097-3099
Author(s):  
Gladiola Tantaru ◽  
Nela Bibire ◽  
Alina Diana Panainte ◽  
Madalina Vieriu ◽  
Mihai Apostu
Keyword(s):  
Schiff Base ◽  
Quantitative Determination ◽  
Absorption Maximum ◽  
Pharmaceutical Products ◽  
Stable Complex ◽  
Complexation Reaction ◽  
Ich Guidelines ◽  
Analytical Reagent ◽  
Detection And Quantification

A new spectrophotometric method for the quantitative determination of Fe (III) was established based on the complexation reaction with a new bis-Schiff base, 4,4`-methylenebis-salicylidene aniline, when a stable complex with an absorption maximum at 520 nm was obtained. The conditions of the complexation reaction were established and the method was validated according to ICH guidelines in terms of linearity, accuracy, precision of the method and the limits of detection and quantification were determined. The method was applied with good results for the quantitative determination of Fe (III) in pharmaceutical products.

scholarly journals A reliable HPLC-DAD method for simultaneous determination of related substances in TBI-166 active pharmaceutical ingredient

2020 ◽  
Vol 32 (2) ◽  
pp. 80-85
Author(s):  
Tingting Zhang ◽  
Wanting Yin ◽  
Bo Jin ◽  
Tong Li ◽  
Chen Ma
Keyword(s):  
High Performance ◽  
Correlation Coefficients ◽  
Active Pharmaceutical Ingredient ◽  
Gradient Elution ◽  
Reversed Phase ◽  
Phase System ◽  
Related Substances ◽  
Ich Guidelines ◽  
Bulk Drug

A sensitive, stability-indicating reversed-phase high-performance liquid chromatography with diode array detection (HPLC–DAD) method has been developed for the determination of TBI-166 and its 10 kinds of related impurities. Chromatographic separation was achieved on a Kromasil ODS column (250 mm × 4.6 mm, 5 μm), with a gradient elution of the mobile phase system consisting of acetonitrile and 1% ammonium formate solution (with 0.2% formic acid). The flow rate was 1.0 mL/min, and the detection wavelength was set at 251 nm. The method was validated according to the International Conference on Harmonization (ICH) guidelines with respect to selectivity, linearity, limits, accuracy, precision, and robustness. The calibration curves were linear from LOQ to 150% of the specification limit of impurity with correlation coefficients not less than 0.999. The limits of quantitation were between 0.123 and 0.257 μg/mL. Accuracy for the related substances was estimated by the recovery ranged from 94.6% to 111.2%. The method was proved to be reliable for the determination of related substances in TBI-166 bulk drug, which is essential and important in the quality control.

scholarly journals ICP-OES elemental impurities study on different pharmaceutical dosage forms of Ibuprofen using microwave-assisted digestion procedure

2021 ◽  
Vol 40 (1) ◽  
pp. 35
Author(s):  
Katerina Jancevska ◽  
Gjorgji Petrushevski ◽  
Mirjana Bogdanoska ◽  
Trajce Stafilov ◽  
Sonja Ugarkovic
Keyword(s):  
Correlation Coefficients ◽  
Dosage Forms ◽  
Regression Equations ◽  
Icp Oes ◽  
Pharmaceutical Dosage Forms ◽  
Digestion Procedure ◽  
Microwave Assisted ◽  
Elemental Impurities ◽  
Microwave Assisted Digestion

Fast and simple closed-vessel microwave-assisted digestion procedure was developed for decomposition of three pharmaceutical dosage forms of ibuprofen such as tablets, suspension and gel, prior to elemental impurity analysis by one robust and precise ICP-OES method. Samples were digested by four-step microwave program consisting of a 10 min temperature gradient to 180°C, maintained at 180°C for 10 min, followed by 5 min ramping time to 210°C with holding time of 10 min on 210°C. Subsequently, ICP-OES method was developed and validated for simultaneous determination of selected elemental impurities. Results of recovery studies range between 77% and 105% for each element in all analyzed formulations. Correlation coefficients of the regression equations were higher than 0.999 for all analyzed elements. Validation results reveal that the proposed method is specific, accurate, and precise and could be applied for simultaneous quantitative analysis of multi element solutions in different pharmaceutical dosage forms of ibuprofen.

scholarly journals Validated RP-HPLC Method for the Determination of Ivabradine Hydrochloride in Pharmaceutical Formulation

2017 ◽  
Vol 9 (05) ◽  
Author(s):  
MD. Muzaffar -ur- Rehman1 ◽  
G. Nagamallika
Keyword(s):  
Mobile Phase ◽  
Dosage Forms ◽  
Hplc Method ◽  
Pharmaceutical Formulation ◽  
Intermediate Precision ◽  
Pharmaceutical Dosage Forms ◽  
Rp Hplc ◽  
Ich Guidelines ◽  
Bulk Drug

A simple, rapid, precise, and accurate RP-HPLC method for the estimation of Ivabradine Hydrochloride an anti-anginal agent, both as a bulk drug and in pharmaceutical formulation was developed. The chromatographic separation was achieved on a Thermosil C18 150 × 4.5 mm, 5μm column by using a mobile phase containing a mixture of methanol and phosphate buffer pH 6.5 in the ratio of 65:35 % v/v at a flow rate of 1ml/min and at an ambient temperature. The detection was monitored at a wavelength of 265nm. A clear chromatographic peak was identified with the retention time of 4.36 min and tailing factor of 1.23. The developed method was validated according to ICH guidelines with respect to specificity, linearity, accuracy, precision and robustness. The method shows a good linear relationship with correlation co-efficient of more than 0.992 in the concentration range of 30μg-150μg. The method showed mean % Recovery of 100.4% and %RSD for repeatability and intermediate precision was less than 2%. The proposed method can be used successfully for the quantitative determination of Ivabradine HCL in pharmaceutical dosage forms.

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