Performance Characteristics of Methods of Analysis Used for Regulatory Purposes. I. Drug Dosage Forms. F. Gravimetric and Titrimetric Methods

1988 ◽  
Vol 71 (3) ◽  
pp. 619-635 ◽  
Author(s):  
Michel Margosis ◽  
William Horwitz ◽  
Richard Albert
Keyword(s):  
Pharmaceutical Preparations ◽  
Drug Dosage ◽  
Drug Analysis ◽  
Dosage Forms ◽  
Fractional Concentration ◽  
Collaborative Studies ◽  
Relative Standard ◽  
The Difference ◽  
Instrumental Methods ◽  
Best Fit

Abstract The original gravimetric and titrimetric methods approved by AOAC for the analysis of pharmaceutical preparations, particularly during the period 1915-1950, show precision, recovery, and outlier parameters approximately the same as those exhibited by the previously reviewed instrumental methods that are currently used. Fifty-nine published collaborative studies utilized gravimetric methods and 85 used titrimetric. The studies of the gravimetric methods encompassed 47 analytes, 95 dosage forms, and 136 assays; the corresponding figures for the titrimetric studies are 72, 112, and 152. An average of approximately 7 laboratories participated per study. The line of best fit of the relative standard deviation between-laboratories (RSDR) plotted against the negative logarithm of the fractional concentration, C, extends from 1.2 and 1.0% for the gravimetric and titrimetric methods, respectively, at 100% concentration to 2.2 and 2.8% at 1.0% concentration. Below this concentration the precision of the titrimetric methods degenerates faster than that of the gravimetric methods. Above about 0.1% concentration the gravimetric and titrimetric methods are somewhat more precise than the instrumental methods in current use for drug analysis. The difference, however, is not statistically significant and the general equation, RSDR = 2 exp(l - 0.5 log C), is also applicable to gravimetric and titrimetric methods above a concentration level of about C = 0.001 (0.1%)

Performance Characteristics of Methods of Analysis Used for Regulatory Purposes. I. Drug Dosage Forms. E. Miscellaneous Methods

1985 ◽  
Vol 68 (5) ◽  
pp. 830-838
Author(s):  
William Horwitz ◽  
Richard Albert
Keyword(s):  
Standard Deviation ◽  
Relative Standard Deviation ◽  
General Relation ◽  
Drug Dosage ◽  
Dosage Forms ◽  
Allergenic Protein ◽  
Collaborative Studies ◽  
Relative Standard ◽  
Instrumental Methods ◽  
Best Fit

Abstract Precision parameters of miscellaneous methods for the analysis of drug dosage forms approved by AOAC since 1972, and not previously reviewed in this series, were recalculated on a consistent statistical basis by using the computer program FDACHEMIST. Seventeen published collaborative studies were reviewed; the studies encompassed 19 analytes in 80 different materials (dosage forms), 102 collaborative assays, approximately 10 laboratories per study, and principally direct spectrophotometric, polarographic, and spectroscopic methods, for a total of 1451 determinations. The average repeatability relative standard deviation (within-laboratories, RSD„) for the instrumental methods was 1.5%; the reproducibility relative standard deviation (among-laboratories, including within-, RSDX) was 2.6%; the ratio RSD„/RSDX of the averages was 0.57, with an average outlier rate of 2.7% of the reported determinations. The line of best fit of RSDX for the instrumental methods plotted against the negative logarithm of the concentration increases slightly with decreasing concentration, extending from an RSDX of approximately 2.0% at 100% concentration to an RSDX of 3.4% at 0.001% (10 ppm) concentration; this represents an RSDX change of approximately 0.3% (absolute) for each 10-fold decrease in concentration, independent of analyte, matrix, and method. A method for determining precipitated allergenic protein by the micro-Kjeldahl technique appeared to be outside this general relation, showing an RSDX of about 13% at a concentration of 0.015% (150 ppm) nitrogen.

Performance Characteristics of Methods of Analysis Used for Regulatory Purposes. I. Drug Dosage Forms. C. Automated Methods

1985 ◽  
Vol 68 (1) ◽  
pp. 112-121
Author(s):  
William Horwitz ◽  
Richard Albert
Keyword(s):  
Computer Program ◽  
Drug Dosage ◽  
Dosage Forms ◽  
Performance Characteristics ◽  
Methods Of Analysis ◽  
Collaborative Studies ◽  
Relative Standard ◽  
Standard Deviations ◽  
Best Fit ◽  
Automated Methods

Abstract For analysis of drug dosage forms, precision measures of AOAC approved automated methods, usually containing a spectrophotometric or fluorometric measurement step, were recalculated on a consistent statistical basis, using a computer program "FDACHEMIST." Ten collaborative studies of 14 compounds in 38 materials, consisting of various dosage forms, usually in 10 replications by an average of 7 laboratories, with a total of 2461 determinations, were reviewed. The average relative standard deviations within-laboratory (RSD0) and among-laboratories (RSDX) were 1.1 and 1.9%, respectively, and the ratio of RSD„/RSDX was 0.57, with an average outlier rate of 0.57% of the reported values. The line of best fit for RSDX plotted against — log concentration increases slightly with decreasing concentration, extending from an RSDX of about 1.6% at 100% concentration to an RSDX of 2.2% at 0.1% concentration, a change in RSDX of about 0.2% for a 10-fold decrease in concentration, independent of analyte and matrix.

Performance Characteristics of Methods of Analysis Used for Regulatory Purposes. I. Drug Dosage Forms. B. Gas Chromatographic Methods

1984 ◽  
Vol 67 (3) ◽  
pp. 648-652
Author(s):  
William Horwitz ◽  
Richard Albert
Keyword(s):  
Coefficient Of Variation ◽  
Internal Standard ◽  
Drug Dosage ◽  
Dosage Forms ◽  
Chromatographic Methods ◽  
Collaborative Studies ◽  
Simple Extraction ◽  
Standard Solution ◽  
Best Fit

Abstract Gas chromatographic methods for the analysis of drug dosage forms consist of a simple extraction, dilution with an internal standard solution, and injection, or, even simpler, dilution with the internal standard solution and injection. These methods were used in 7 collaborative studies of the determination of 12 pharmaceuticals, published in the Journal of the AOAC during 1973–1983. A total of 43 individual materials consisting of various dosage forms were each analyzed, usually in duplicate, by an average of 8 laboratories, with a total of 582 reported determinations. The average within-laboratory coefficient of variation (CVo) was 1.25% and the average among-laboratories coefficient of variation (CVx) was 2.41%, for a CVo/CVx ratio of 0.52, at an average outlier rate of 1.4% of the reported values. The line of best fit for CVx plotted against concentration increases with decreasing concentration, extending from a CVx of approximately 1.8% at 100% concentration to a CVx of approximately 3.2% at 1% concentration. The change in CVx for a 10-fold decrease in concentration is approximately 0.7% CVx, independent of analyte and matrix.

Performance Characteristics of Methods of Analysis Used for Regulatory Purposes.I. Drug Dosage Forms. D. High Pressure Liquid Chromatographic Methods

1985 ◽  
Vol 68 (2) ◽  
pp. 191-198 ◽  
Author(s):  
William Horwitz ◽  
Richard H Albert
Keyword(s):  
High Pressure ◽  
Standard Deviation ◽  
Relative Standard Deviation ◽  
Drug Dosage ◽  
Dosage Forms ◽  
High Pressure Liquid Chromatographic ◽  
Chromatographic Methods ◽  
Collaborative Studies ◽  
Relative Standard ◽  
Liquid Chromatographic

Abstract Precision parameters of high pressure liquid chromatographic methods approved by AOAC for the analysis of drug dosage forms were recalculated on a consistent statistical basis, using the computer program "FDACHEMIST." Eleven collaborative studies of 12 compounds in 66 dosage forms analyzed by an average of 9 laboratories per study, with a total of 1150 determinations, were reviewed. For the approved methods and methods awaiting approval (9 studies, 11 compounds, 54 dosage forms, and 959 determinations), the average repeatability relative standard deviation (within-laboratory; RSDo) was 1.0%; reproducibility relative standard deviation (among-laboratories, including within-; RSDX) was 2.5%; the ratio RSD„/RSDX was an unusually low 0.40, with an average outlier rate of 0.6% of the reported values. The line of best fit for RSDX plotted against — log concentration increases with decreasing concentration, extending approximately from RSDX =2% at 100% concentration to RSDX = 3.6% at 0.01% concentration,a change in RSDX of about 0.4% for each 10-fold decrease in concentration,independent of analyte and matrix.

Simultaneous Spectrophotometric Determination of Salbutamol by Coupling with Diazotized 4-Aminobenzoic acid

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Hind Hadi ◽  
Gufran Salim
Keyword(s):  
Pharmaceutical Preparations ◽  
Coupling Reaction ◽  
Dosage Forms ◽  
Water Soluble ◽  
Trace Determination ◽  
Aminobenzoic Acid ◽  
Optimum Conditions ◽  
Colored Product ◽  
Versus Concentration

A simple, rapid and sensitive spectrophotmetric method for trace determination of salbutamol (SAL) in aqueous solution and in pharmaceutical preparations is described. The method is based on the diazotization coupling reaction of the intended compound with 4-amino benzoic acid (ABA) in alkaline medium to form an intense orange, water soluble dye that is stable and shows maximum absorption at 410 nm. A graph of absorbance versus concentration indicates that Beer’s law is obeyed over the concentration range of 0.5-30 ppm, with a molar absorbtivity 3.76×104 L.mol-1 .cm-1 depending on the concentration of SAL. The optimum conditions and stability of the colored product have been investigated and the method was applied successfully to the determination of SAL in dosage forms.

ICH/FDA Guidelines-Compliant Validated Stability-Indicating HPLC-UV Method for the Determination of Axitinib in Bulk and Dosage Forms

2020 ◽  
Vol 16 (8) ◽  
pp. 1106-1112
Author(s):  
Ibrahim A. Darwish ◽  
Nasr Y. Khalil ◽  
Mohammad AlZeer
Keyword(s):  
High Performance ◽  
Kinase Inhibitor ◽  
Degradation Products ◽  
Internal Standard ◽  
Dosage Forms ◽  
Uv Detector ◽  
Stability Indicating ◽  
Therapeutic Benefits ◽  
Relative Standard

Background: Axitinib (AXT) is a member of the new generation of the kinase inhibitor indicated for the treatment of advanced renal cell carcinoma. Its therapeutic benefits depend on assuring the good-quality of its dosage forms in terms of content and stability of the pharmaceutically active ingredient. Objective: This study was devoted to the development of a simple, sensitive and accurate stabilityindicating high-performance liquid chromatographic method with ultraviolet detection (HPLC-UV) for the determination of AXT in its bulk and dosage forms. Methods: Waters HPLC system was used. The chromatographic separation of AXT, internal standard (olaparib), and degradation products were performed on the Nucleosil CN column (250 × 4.6 mm, 5 μm). The mobile phase consisted of water:acetonitrile:methanol (40:40:20, v/v/v) with a flow rate of 1 ml/min, and the UV detector was set at 225 nm. AXT was subjected to different accelerated stress conditions and the degradation products, when any, were completely resolved from the intact AXT. Results: The method was linear (r = 0.9998) in the concentration range of 5-50 μg/ml. The limits of detection and quantitation were 0.85 and 2.57 μg/ml, respectively. The accuracy of the method, measured as recovery, was in the range of 98.0-103.6% with relative standard deviations in the range of 0.06-3.43%. The results of stability testing revealed that AXT was mostly stable in neutral and oxidative conditions; however, it was unstable in alkaline and acidic conditions. The kinetics of degradation were studied, and the kinetic rate constants were determined. The proposed method was successfully applied for the determination of AXT in bulk drug and dosage forms. Conclusions: A stability-indicating HPLC-UV method was developed and validated for assessing AXT stability in its bulk and dosage forms. The method met the regulatory requirements of the International Conference on Harmonization (ICH) and the Food and Drug Administration (FDA). The results demonstrated that the method would have great value when applied in quality control and stability studies for AXT.

scholarly journals Validation of a Method Based on Triglycerides for the Detection of Low Percentages of Hazelnut Oil in Olive Oil by Column Liquid Chromatography

2007 ◽  
Vol 90 (5) ◽  
pp. 1346-1353 ◽  
Author(s):  
Diego L García-González ◽  
María Viera-Macías ◽  
Ramón Aparicio-Ruiz ◽  
Maria T Morales ◽  
Ramón Aparicio
Keyword(s):  
Liquid Chromatography ◽  
Olive Oil ◽  
Carbon Number ◽  
Hazelnut Oil ◽  
Equivalent Carbon Number ◽  
Experimental Conditions ◽  
Mathematical Algorithm ◽  
Relative Standard ◽  
Triglyceride Content ◽  
The Difference

Abstract The difference between theoretical and empirical triglyceride content is a powerful tool to detect the presence of any vegetable oil in olive oil. The current drawback of the method is the separation between equivalent carbon number ECN42 compounds, which affects the reliability of the method and, hence, its cutoff limit. The determination of the triglyceride profile by liquid chromatography using propionitrile as the mobile phase has recently been proposed to improve their quantification, together with a mathematical algorithm whose binary response determines the presence or absence of hazelnut oil. Twenty-one laboratories from 9 countries participated in an interlaboratory study to evaluate the performance characteristics of the whole analytical method. Participants analyzed 12 samples in duplicate, split into 3 intercomparison studies. Statistically significant differences due to the experimental conditions were found in some laboratories, which were detected as outliers by use of Cochran's and Grubbs' tests. The relative standard deviations (RSD) for repeatability and reproducibility were determined following the AOAC Guidelines for Collaborative Studies. The analytical properties of the method were determined by means of the sensitivity (0.86), selectivity (0.94), and reliability (72) for a cutoff limit of 8 (probability 94).

Total Pressure Correction of a Sub-Miniature Five-Hole Probe in Areas of Pressure Gradients

2012 ◽  
Author(s):  
J. Town ◽  
A. Akturk ◽  
C. Camcı
Keyword(s):  
Pressure Measurement ◽  
Measurement Errors ◽  
Total Pressure ◽  
Pressure Gradients ◽  
Pressure Data ◽  
Flow Conditions ◽  
Complex Flow ◽  
Ducted Fan ◽  
The Difference ◽  
Best Fit

Five-hole probes, being a dependable and accurate aerodynamic tools, are excellent choices for measuring complex flow fields. However, total pressure gradients can induce measurement errors. The combined effect of the different flow conditions on the ports causes the measured total pressure to be prone to a greater error. This paper proposes a way to correct the total pressure measurement. The correction is based on the difference between the measured total pressure data of a Kiel probe and a sub-miniature prism-type five-hole probe. By comparing them in a ducted fan related flow field, a line of best fit was constructed. The line of best fit is dependent on the slope of the line in a total pressure versus span and difference in total pressure between the probes at the same location. A computer program, performs the comparison and creates the correction equation. The equation is subsequently applied to the five-hole probe total pressure measurement, and the other dependent values are adjusted. The validity of the correction is then tested by placing the Kiel probe and the five-hole probe in ducted fans with a variety of different tip clearances.

scholarly journals Comparison of anterior retraction and anchorage control between en masse retraction and two-step retraction: A randomized prospective clinical trial

2018 ◽  
Vol 89 (2) ◽  
pp. 190-199 ◽  
Author(s):  
Patricia Pigato Schneider ◽  
Luiz Gonzaga Gandini Júnior ◽  
André da Costa Monini ◽  
Ary dos Santos Pinto ◽  
Ki Beom Kim
Keyword(s):  
Clinical Trial ◽  
Treatment Group ◽  
Secondary Outcome ◽  
Space Closure ◽  
The Difference ◽  
Maxilla And Mandible ◽  
Anchorage Loss ◽  
Bimaxillary Protrusion ◽  
Best Fit ◽  
En Masse Retraction

ABSTRACT Objectives: The purpose of this two-arm parallel trial was to compare en masse (ER) and two-step retraction (TSR) during space closure. Materials and Methods: Forty-eight adult patients with bimaxillary protrusion who were planned for treatment with extraction of four first premolars were enrolled. All patients were randomly allocated in a 1:1 ratio to either the ER (n = 24) group or the TSR (n = 24) group. The main outcome was the amount of posterior anchorage loss in the molars and the retraction of the incisors between ER and TSR; the difference in incisor and molar inclination was a secondary outcome. Lateral cephalometric radiographs and oblique cephalometric radiographs at 45° were taken before retraction (T1) and after space closure (T2). Cephalograms were digitized and superimposed on the anatomic best fit of the maxilla and mandible by one operator who was blinded to the treatment group. Results: Neither incisor nor molar crown movements showed any significant differences between the ER and TSR. There were no significant differences in the tipping of incisors and molars between the two groups. Conclusions: No significant differences existed in the amount of retraction of incisors and anchorage loss of molars between ER and TSR. Changes in incisor and molar tipping were similar, with the crowns showing more movement than the apex.

scholarly journals Application of Liquid Chromatography to the Simultaneous Determination of Acetylsalicylic Acid, Caffeine, Codeine, Paracetamol, Pyridoxine, and Thiamine in Pharmaceutical Preparations

2001 ◽  
Vol 84 (3) ◽  
pp. 676-683 ◽  
Author(s):  
Natividad Ramos-Martos ◽  
Francisco Aguirre-Gómez ◽  
Antonio Molina-Díaz ◽  
Luis F Capitán-Vallvey
Keyword(s):  
Salicylic Acid ◽  
Acetylsalicylic Acid ◽  
Simultaneous Determination ◽  
Pharmaceutical Preparations ◽  
Reversed Phase ◽  
Liquid Chromatographic Method ◽  
Relative Standard ◽  
Phase Liquid ◽  
Liquid Chromatographic

Abstract This paper describes a rapid reversed-phase liquid chromatographic method, with UV detection, for the simultaneous determination of acetylsalicylic acid, caffeine, codeine, paracetamol, pyridoxine, and thiamine in pharmaceutical preparations. A reversed-phase C18 Nucleosil column is used. The mobile phase consists of 2 successive eluants: water (5 min) and acetonitrile–water (75 + 25, v/v; 9 min), both adjusted to pH 2.1 with phosphoric acid. Before determination acetylsalicylic acid is completely converted to salicylic acid by alkaline hydrolysis. Salicylic acid, caffeine, paracetamol, pyridoxine, and thiamine are all detected at 285 nm, whereas codeine is detected at 240 nm. Calibration curves were linear for salicylic acid, caffeine, paracetamol, and pyridoxine in the range of 50–500 mg/L, and for codeine and thiamine in the range of 50–1000 mg/L. The method was applied to the analysis of 13 fortified commercial pharmaceutical preparations. Recoveries ranged from 92.6 to 105.5%, with relative standard deviations of 1.1–5.8%.

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