Applikationer

This poster presented jointly with USP at AAPS meeting shows, that we successfully developed and validated a single IC procedure for potassium assay and identification in potassium bicarbonate and potassium chloride for effervescent oral suspension. The optimized chromatographic conditions could be used for other cationic impurities, such as magnesium, calcium, sodium, and ammonium in potassium bicarbonate and potassium chloride for effervescent oral suspension. Single chromatographic method for assay and identification simplifies the overall QA/QC workflow.

This poster presented jointly with USP at AAPS meeting shows, that we successfully validated an IC method to determine chloride and sulfate in drug substances, potassium bicarbonate and potassium carbonate. The proposed IC method overcomes limitations of the turbidimetry/visual comparison methods.

Potassium iodide (KI) is used to treat overactive thyroid and to protect the thyroid gland from the effects of radiation from inhaled or swallowed radioactive iodine. Currently, in the USP Potassium Iodide Monograph, iodide identification is performed by wet chemistry and assay by manual titration, which has a history of reduced precision and accuracy. As part of USP’s global monograph modernization initiative, an alternative selective and sensitive method was developed and validated – ion chromatography (IC). The proposed IC method can also be used for the identification test as an alternative to wet chemistry.

Fluoride is commonly used in dental products to help prevent tooth decay. When fluoride is present in high concentrations, these products are regulated by 21 CFR 355. Three fluoride compounds used in over the counter (OTC) anti‐cavity dental products are sodium fluoride, stannous fluoride and sodium monofluorophosphate (MFP). The assay of fluoride in these active ingredients and finished formulations are determined by manual titration, or by ion‐selective electrodes. As a part of USP’s global monograph modernization initiative, an alternative selective and sensitive method has been developed and validated – ion chromatography (IC). The proposed IC method can also be used for the identification test as an alternative to the wet chemistry method.

Within the scope of the USP monograph modernization, potassium is determined in potassium bitartrate applying cation chromatography with direct conductivity detection. The USP41 monograph for “Potassium bitartrate” does not yet mention an assay for potassium. The separation is performed on a Metrosep C 6 - 150/4.0 column (L76). The assay of potassium is performed with two commercially available products according to USP definitions. All acceptance criteria are fulfilled.

Within the scope of the USP monograph modernization, potassium is determined in potassium sodium tartrate applying cation chromatography with direct conductivity detection. The USP41 monograph for “Potassium sodium tartrate” does not yet mention an assay for potassium. The separation is performed on a Metrosep C 6 - 150/4.0 column (L76). The assay of potassium is performed with two commercially available products according to USP definitions. All acceptance criteria are fulfilled.

Within the scope of the USP monograph modernization, potassium is determined in potassium bicarbonate effervescent tablets for oral suspension applying cation chromatography with direct conductivity detection. The separation is performed on a Metrosep C 6 - 150/4.0 column (L76). All acceptance criteria are fulfilled.

As an alternative to flame photometry, ion chromatography with non-suppressed conductivity detection has been approved by the USP as a validated method to quantify potassium and sodium content in potassium and sodium bicarbonates and citric acid effervescent tablets for oral solution. The present IC method has been validated according to USP General Chapter <621>.

As an alternative to flame photometry, ion chromatography with non-suppressed conductivity detection has been approved by the USP as a validated method to quantify potassium content in potassium bicarbonate and potassium chloride effervescent tablets for oral solution. The Metrosep C 6 - 150/4.0 column (L76) provides the required separation of potassium and magnesium. The present IC method has been validated according to USP General Chapter <621>.

Within the scope of the USP monograph modernization, sodium is determined in potassium sodium tartrate applying cation chromatography with direct conductivity detection. The USP41 monograph for «Potassium sodium tartrate» does not yet mention an assay for sodium. The separation is performed on a Metrosep C 6 - 150/4.0 column (L76). The assay of potassium is performed with two commercially available products according to USP definitions. All acceptance criteria are fulfilled. See AN-C-182 for the respective determination of potassium. Apllying this method allows to determine sodium and potassium simultaneously according to USP.

Potassium bitartrate for pharmaceutical use must comply with USP requirements. The actual monograph (USP 42) uses a colorimetric method for the determination of ammonium impurities. Ion chromatography allows the measurement in a single determination under the same conditions used for the potassium assay (see AN-C-181). In the course of the USP monograph modernization, this ion chromatographic approach makes this type of analysis even easier.

Calcium carbonate has a wide applicability in the pharmaceutical industry as an excipient and also as an active ingredient, and in the food industry as a major dietary supplement. The U.S. Pharmacopoeia (USP) monographs for calcium and magnesium carbonates tablets as well as calcium carbonate and magnesia chewable tablets currently describe manual titration as the assay procedure for calcium and magnesium. The USP has embarked on a global initiative to modernize many of the existing monographs across all compendia. In response to this initiative, two alternative analytical methods were developed to determine the analytes calcium and magnesium. This Application Note presents ion chromatography (IC) procedures using conductivity detection that provide better accuracy and specificity and are suitable for the intended purpose. These validated IC methods (according to USP General Chapter <1225>) offer a significant improvement to the existing assays because they can simultaneously determine both analytes calcium and magnesium, saving both time and effort.

Potassium citrate and citric acid oral solutions act as systemic alkalizers. Potassium assays, validated per USP <621> and <1225>, use IC with L76 cation-exchange columns.

The assay of calcium acetate, often used as a phosphate binder for dialysis patients, can be performed with ion chromatography (IC) as per USP <621> and <1225>.

Succinylcholine is a short-term paralyzing agent used e.g., for tracheal intubation. Choline is a building block of the drug and needs to be determined as an impurity. USP applies cation chromatography with conductivity detection after suppression. Eluent composition and column type do not exactly comply with the USP method. However, the results fulfill the respective requirements. The choline concentration of the sample is out of USP specifications.

Compounded injections of sodium bicarbonate are sterile solutions for correcting metabolic acidosis and other conditions requiring systemic alkalinization. Compounded injections of sodium phosphates serve as a phosphate source to either prevent or correct hypophosphatemia in patients with restricted oral intake. Ion chromatography (IC) with suppressed conductivity detection is the standardized way to accurately quantify sodium in these solutions.

This Application Note shows how easy it is to determine water content in the pharmaceutical excipient lactose with reagent-free near-infrared spectroscopy.

Gentamicin is an aminoglycoside antibiotic and is composed of a number of related gentamicins. It is applied for several types of infections. For the determination of the major components, USP asks for chromatographic separation with pulsed amperometric detection using a gold working electrode. A post-column addition of NaOH is performed prior to the detection.

Pamidronate is applied to treat osteoporosis by strengthening the bones. It is a bisphosphonate containing a primary amine group. Phosphite and phosphate are related compounds, which need to be quantified. USP requires the use of formic acid eluent with refractive index detection. But a standard IC procedure offers an alternative with better sensitivity. Phosphite and phosphate are analyzed with conductivity detection after sequential suppression.

Within the scope of the modernization of USP, chloride and sulfate are determined as impurities in potassium hydrogen carbonate (bicarbonate). USP41 monograph for potassium bicarbonate does not check for chloride and sulfate. Applying ion chromatography with conductivity detection after sequential suppression allows quantifying these impurities.

Potassium chloride and potassium bicarbonate effervescent tablets are used to prevent potassium deficiency. Pharmaceutical manufacturers and labs adhere to strict quality regulations using USP-NF monographs. Ion chromatography with suppressed conductivity detection, utilizing the Metrosep A Supp 16 - 100/4.0 (L91) column, is approved by the USP to quantify chloride content in these tablets, following validation per USP General Chapter <621>.

Fluoride is commonly used in dental products to help prevent tooth decay. If the products are intended to prevent the formation of cavities (carries), then it is regulated by the US Food and Drug Administration (USFDA) as an Over-the-Counter (OTC) Drug. Previously, the assay of Fluoride in oral solution was done by Ion selective electrode and identification was done by tedious wet chemistry method. USP has updated this monograph for Assay and identification tests with Ion Chromatography using L46 packing. The Metrosep A Supp 1 - 250/4.6 column fulfills all USP acceptance criteria. It therefore is a viable alternative separation column for the determination of sodium fluoride in oral solutions.

Dental care products often contain sodium fluoride as an active ingredient. Manufacturers use the United States Pharmacopeia and National Formulary (USP-NF) Monograph «Sodium Fluoride» to quantify sodium fluoride and its anionic contaminants chloride and acetate in these products. The validated USP method proposes ion chromatography (IC) with suppressed conductivity detection to carry out the fluoride assay as well as the impurity determination in a single chromatogram.

Sodium fluoride gel for pharmaceutical use needs to comply with USP requirements. The actual monograph (USP 42) uses two different methods for the identification and the assay. Ion chromatography allows the analysis of these two parameters in one single determination. In the course of the USP monograph modernization, this ion chromatographic approach makes this type of analysis even easier.

Stannous fluoride gel for pharmaceutical use needs to comply with USP requirements. The actual monograph (USP 42) utilizes two different methods for the identification and the assay. Ion chromatography allows the analysis of these two parameters within a single determination. In the course of the USP monograph modernization, this ion chromatographic approach makes this type of analysis even easier.

Sodium fluoride and phosphoric acid gel for pharmaceutical use need to comply with USP requirements. The actual monograph (USP 42) uses two different methods for the identification and the assay. Ion chromatography allows the measurement of these two parameters within a single determination. In the course of the USP monograph modernization, this ion chromatographic approach makes this type of analysis even easier.

In the course of USP column equivalency tests, the Metrosep A Supp 3 - 250/4.0 is applied for the assay of citric acid/citrate and phosphate according to USP general Chapter <345>. This report shows that the Metrosep A Supp 3 - 250/4.0 column is equivalent to packing L61 required in USP general Chapter <345>.

As an alternative to titration, ion chromatography (IC) with suppressed conductivity detection has been approved by USP as validated method to quantify chloride content in NaCl tablets for solution or oral use.

An ion chromatography (IC) assay with suppressed conductivity detection is the standardized way to accurately quantify phosphate in phosphates compounded injections.

Anticavity pharmaceuticals like sodium fluoride and acidulated phosphate topical solution products require strict quality control. This Application Note outlines the fluoride IC assay as described in the USP Monograph Sodium Fluoride and Acidulated Phosphate Topical Solution.

In severe cases of cyanide poisoning, sodium nitrite is used along with sodium thiosulfate for treatment. This Application Note describes the nitrite ion chromatography assay with the Metrosep A Supp 4 column and suppressed conductivity detection. This column equivalency study was in cooperation with the USP according to the USP General Chapter <621>.

Nitrosamine presence in medicines, even at trace level poses high safety risks to patients (carcinogenic). Nitrosamine formation can be avoided by controlling and monitoring the nitrite concentration in pharmaceutical products and substances. This Application Note describes the analysis of nitrite in duloxetine hydrochloride with ion chromatography (IC).

Nitrosamine formation can be avoided by controlling the nitrite concentration in pharmaceutical products and processes. To monitor nitrosamine formation, sensitive analytical methods such as ion chromatography for the determination of nitrite in pharmaceutical products and substances are essential.

This Application Note describes the photometric determination of zinc sulfate using the Optrode at a wavelength of 610 nm. Complexometric titration of zinc requires EDTA as titrant and Eriochrome Black T as indicator. The method fully complies with Ph. Eur. and USP.

Potassium carbonate and potassium bicarbonate are important raw materials in the pharmaceutical industry. As APIs, both can be used in effervescent tablets and powders as supplements to help patients with low potassium levels in their blood.For both species, the other species is the most important contamination. For the assay, a selective method is thus required. Separation of both species by ion chromatography is not possible as the eluent changes the ratio of carbonate and bicarbonate falsifying the result. Due to their different pKa values, carbonate and hydrogen carbonate can be selectively determined by titration, which is therefore the method of choice for pharmacopeias, such as the USP and Ph.Eur.Using potentiometric autotitration instead of manual titration increases the accuracy and reliability of results. Furthermore, the use of an autotitrator ensures that crucial requirements of regulatory compliance guidelines such as dataintegrity are met.

Sodium lactate is a salt form of lactic acid used in many regulated industries—therefore an accurate determination of the lactate content is required and is already covered in several norms. One such monograph by the US Pharmacopoeia (USP) results in high accuracies and well-defined titration curves but uses titrants and solvents that are more costly than necessary. In comparison, the presented modified method from Metrohm requires a 1:1 mixture of water and acetone and uses aqueous hydrochloric acid as titrant, resulting in an estimated cost reduction of 40% per titration compared to the USP method (USP–NF 2021, Issue 2). Furthermore, the time needed for each analysis is reduced to just 12% of the USP method (excluding blank determination). This Application Note presents both methods to determine lactate content and shows the results obtained on an OMNIS system.

Iron sucrose injection is a dark brown liquid which contains sucrose and iron(III) hydroxide in an aqueous solution, commonly used for the treatment of iron deficiency anemia. As a medical product, iron sucrose is subject to strict controls. Among other tests, the U.S. Pharmacopeia (USP) requires to monitor the limit of Fe(II) in the iron sucrose injection solution by polarography. The benefit of polarography is that Fe(II) and Fe(III) show signals at different potentials, and therefore an easier determination of Fe(II) without a previous separation of the two oxidation states is possible. The 884 Professional VA together with the viva software allows a straightforward determination of the Fe(II) content of iron sucrose injection solution following the requirements of the USP. The Fe(II) content is automatically calculated and stored in a database together with all relevant determination and calculation parameters.

Accurate iodine determination in thyroid tablets, ensuring treatment efficacy, is achieved using the 884 Professional VA and Multi-Mode Electrode pro per USP guidelines.

The objective of validation of an analytical procedure is to demonstrate that it is suitable for its intended purpose. Recommendations for the validation of analytical methods can be found in ICH Guidance Q2(R1) Validation of Analytical Procedures: Text and Methodology and in USP General Chapter <1225> Validation of Compendial Procedures. The goal of this white paper is to provide some recommendations for the validation of titration methods.