Aplikace

Raman spectroscopy is used for material characterization by analyzing molecular or crystal symmetrical vibrations and rotations that are excited by a laser, and exhibit vibrations specific to the molecular bonds and crystal arrangements in the molecules. Raman technology is a valuable tool in distinguishing different polymorphs. Examples of portable Raman spectroscopy for identification of polymorphs and in monitoring the polymorphic transiton of citric acid and its hydrated form are presented.

Raman spectroscopy is an advantageous analytical tool that allows for the measurement of molecular structure and identifying chemical composition of materials based on the rotational and vibrational modes of a molecule. With advanced technology and an optimized optical design, the B&W Tek BAC102 series E-grade probe can access lower frequency modes down to 65 cm-1, providing key information for applications in protein characterization, polymorph detection, and identification, along with material phase and structure determination.

The NanoRam is able to test material through multiple layers of transparent plastic bags. Postive identification of material on PE bags from 1 to 9 layers were obtained, demonstrating minimum interference from the PE bags on the material identification result.

A new Raman system design is presented that expands the applicability of Raman to See Through diffusely scattering media such as opaque packaging materials, as well as to measure the Raman spectrum and identify thermolabile, photolabile, or heterogeneous samples.

Today’s Raman instrumentation is faster, more rugged, and less expensive than previous instrumentation.The design of high performance, portable and handheld devices has introduced the technology to new application areas that were previously not possible with older, more cumbersome instruments. Handheld Raman instruments such as the NanoRam® from B&W Tek are well-suited for pharmaceutical applications such as the testing of raw materials, verification of final products and the identification of counterfeit drugs due to the technique’s extremely high molecular selectivity.

See through Raman Spectroscopy (STRaman®) is a newly developed technology that expands the capability of Raman spectroscopy to measure samples beneath diffusely scattering packaging material. The STRaman technology features a much larger sampling area than the confocal approach. This design enhances the relative intensity of the signal from the deeper layers, thereby increasing the effective sampling depth, allowing the measurement of material inside visually opaque containers. The larger sampling area has the additional advantage of preventing sample damage by reducing the power density, as well as improving measurement accuracy by eliminating heterogeneous effect.

The two most common mathematical representations used with handheld Raman spectroscopy as decision-making tools for spectroscopic data: Hit Quality Index (HQI) and significance level (p-value) are presented.

The combination of Raman spectroscopy and vapor sorption techniques provides a comprehensive understanding of vapor-solid interactions of pharmaceutical materials as it relates to the structural properties.This paper investigates the in-situ monitoring of a moisture-induced polymorphic transformation (D-mannitol from delta to beta form) using a combined Raman-vapor sorption technique.

This technical note is to demonstrate the NanoRam material identification through dark brown plastic bags. NanoRam is shown to work for material identification inside dark brown polyvinyl bag.

Handheld Raman is used for raw material testing of different sample types and forms. The use of optimized sampling accessories enhances the utility of handheld Raman without compromising data quality or complicating testing.

The RVM method requires only a few spectra to make a model and can be quickly developed on the NanoRam-1064. Multivariate analysis of the Raman spectra on handheld Raman instruments provides more robust methodologies for identifying samples.

Cellulose is a common naturally-derived raw excipient found in the majority of pharmaceutical products. Raw material testing is required to ensure that consumers are receiving quality cellulose and its derivatives. The NanoRam®-1064 is an asset for pharmaceutical identity testing, minimizing fluorescence generated by typical handheld Raman systems with 785 nm lasers. As such, the NanoRam®-1064 is used here to identify cellulose derivatives that would normally fluoresce with a 785 nm laser.

Botanicals are derived from plant materials and used for their medicinal and therapeutic properties in the nutraceuticals market. They are not as heavily regulated by the U.S. Food and Drug Administration (FDA) like the pharmaceuticals drug market, but they are required to follow Good Manufacturing Practice (GMP Requirements).The NanoRam®-1064 is an asset for pharmaceutical identity testing, minimizing fluorescence generated by typical handheld Raman systems with 785 nm lasers. As such, the NanoRam®-1064 is used here to identify botanicals that would normally fluoresce with a 785 nm laser.

Although the process of building, validating and using a method is well-defined through software, the robustness of the method is dependent on proper practice of sampling, validation, and method maintenance. In this document, we will detail the recommended practices for using the multivariate method with NanoRam-1064. These practices are recommended for end users who are in the pharmaceutical environment, and can expand to other industries as well. This document aims to serve as a general reference for NanoRam-1064 users who would like to build an SOP for method development, validation and implementation.

Raman spectroscopy’s use for process analytics in the pharmaceutical and chemical industries continues to grow due to its nondestructive measurements, fast analysis times, and ability to do both qualitative and quantitative analysis. Spectral preprocessing algorithms are routinely applied to quantitative spectroscopic data in order to enhance spectral features while minimizing variability unrelated to the analyte in question. In this technical note we discuss the main preprocessing options pertinent to Raman spectroscopy with real applications examples, and to review the algorithms available in B&W Tek and Metrohm software so that the reader becomes comfortable applying them to build Raman quantitative models.

100% starting materials identification testing is one of the FDA’s directives as per 211.84 for FDA regulated industries such as Pharmaceutical, Vaccines, Cosmetics, Tobacco, Animal veterinary products, Food, etc. STRam®-1064 is a Raman analyzer uniquely suited for this purpose. It measures samples through thick packaging materials such as plastics, multilayer kraft paper sacks, and HDPE containers. A long wavelength laser is used to suppress fluorescence. The ID algorithm isolates the sample signature by subtracting that of the packaging material and compares that with library spectra to achieve identification.

The analytical challenge treated by the present work consists in detecting sub-ppb concentrations of low-molecular-weight amines in the presence of strongly retained cationic drugs by using ion chromatography (IC) with upstream inline coupled-column matrix elimination (CCME). In contrast to direct-injection IC, where the late elution of strongly retained drugs requires eluents with added acetonitrile, the CCME technique uses two preconcentration columns in series. In an «inverse matrix elimination step, cationic drug and target amines are trapped on a high-capacity and a very-high-capacity preconcentration column, respectively. During amine determination, a rinsing solution flushes the drug to waste. This significantly shortens the analysis time and improves sensitivity as well as selectivity. Besides the determination of monomethylamine in Nebivolol hydrochloride discussed here, the CCME technique is a promising tool for detecting further low-molecular-weight amines in a wide range of drugs.

The poster describes the water determination in pharmaceuticals using the Karl Fischer oven technique.

Pharmaceutical analysis guarantees drug safety by providing information on the identity, content, quality, purity, and stability of pharmaceutical products using analytical chemistry. Ion chromatography (IC) offers a broad range of pharmacopeia-compliant applications for quality control, monitoring, and improving drug manufacturing.As a very accurate and versatile technique, IC meets the requirements of many pharmaceutical applications. IC is a USP-accepted standard method for the determination of active pharmaceutical ingredients (APIs), excipients, impurities,pharmaceutical solutions as well as pharmaceutical starting materials, finished pharmaceutical products (FPPs) and even body fluids.This poster describes some typical examples.

Moisture in cannabis impacts potency and must be accurately determined. Loss on drying (LOD) is the most popular method for determining moisture in cannabis. Unfortunately, this technique is not specific to moisture and the loss of any volatile components, such as terpenes, will be incorrectly classified as moisture. Karl Fischer (KF) titration is the only chemically specific test for moisture. This poster describes the instrument used to determine moisture content by Karl Fischer titration and compares the results of this data to loss on drying.

A high throughput automated system was developed to determine pH of culture media using a pH module equipped with an external flow cell. A custom septum-piercing, vented needle was developed to accommodate the shape and size of the customer sample vials. For this application, both accurate and precise pH measurements were required. The data presented in this document was collected by a customer as a part of their validation process and was provided for use with their consent.

This Application Bulletin gives an overview of the coulometric water content determination according to Karl Fischer.Amongst others, it describes the handling of electrodes, samples, and water standards. The described procedures and parameters comply with the ASTM E1064.

As the determination of the exact content of individual glycerides in fats and oils is difficult and time-consuming, several fat sum parameters or fat indices are used for the characterization and quality control of fats and oils. Fats and oils are not only essential for cooking, they are also an important ingredient in pharmaceuticals and personal care products, such as ointments and creams. Consequently, several norms and standards describe the determination of the most important quality control parameters. This Application Bulletin describes eight important analytical methods for the following fat parameters in edible oils and fats:Determination of water content in accordance with the Karl Fischer method; Oxidation stability in accordance with the Rancimat method; Iodine value; Peroxide value; Saponification value; Acid value, free fatty acids (FFA); Hydroxyl number; Traces of nickel using polarography; Special care is taken to avoid chlorinated solvents in these methods. Also, as many of the mentioned methods as possible are automated.

The present Application Bulletin contains NIR applications and feasibility studies using NIRSystems devices in the pharmaceutical industry. Qualitative and quantitative analyses of a wide variety of samples are part of this bulletin. Each application describes the instrument that was originally used for the analysis, as well as the system recommended for the analysis and the results that were achieved thereby.

This Bulletin describes the automatic measurement of conductivity in water samples with low electrical conductivity in accordance with USP<645>. Conductivity measurement is demonstrated on the example of ultrapure water, which is used, among other things, to produce injection solutions in the pharmaceutical sector.

2-amino-N-(2,2,2-trifluoroethyl)-acetamide is a organic building block for synthesis of pharmaceutical products. Its purity is crucial for the success of the respective synthesis step. 2,2,2-trifluoroethylamine, glycine, and inorganic cations are of interest. Their total peak area is required to be < 2 % of the peak area of all peaks above the reporting level. Separation and quantification is achieved on a Metrosep C 4 - 250/4.0 cation column.

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.

Ezetimibe is a cholesterol-reducing drug. It reduces the cholesterol resorption in the small intestine. The molecule holds two fluorophenyl groups. Applying Combustion IC the amount of fluorine in the drug is determined. To avoid an excessive introduction of fluoride into the system, Ezetimibe is dissolved in ethanol prior to the combustion.

Karl Fischer titration can be used to determine the water content in N-acetyl-L-cysteine. Special solvent mixtures can be used to prevent unwanted side reactions in the Karl Fischer titration. The water content of N-acetyl-L-cysteine can thus be determined quickly and accurately, as is shown in this Application Note.

This Application Note shows how, with the help of Vis-NIR spectroscopy and a special plant library, 46 different medicinal and aromatic plants, e.g., Organicum majoricum and Tilia cordata, can be conveniently identified on the basis of their spectrum. In comparison with alternative methods for the determination of plants, which are elaborate and require experienced scientists for their performance, the Vis-NIR method permits rapid and uncomplicated identification.

Sulfathiazoles are sulfonamides with antibiotic effect that occur in various polymorphous forms and that are often used in veterinary medicine. This Application Note shows the differentiation between commercial and sulfathiazole form I using near-infrared spectroscopy (NIRS) with the help of the overtone frequencies of N-H stretching vibration. Form I is the least stable polymorphous form. Crystallization and polymorphism must be monitored as part of quality controls. In this, NIRS is considerably more rapid and more reliable than conventional laboratory methods.

This Application Note shows that visible near-infrared spectroscopy (Vis-NIRS) can be used for the quantification of Baicalin content in herbal supplements. Vis-NIRS is a good alternative to the conventional lab method (HPLC) and can save both cost and time.

The quantification of residual moisture in lyophilized pharmaceutical peptides is an important measure for quality control in the pharmaceutical industry. For development purposes, such measurements are necessary and routinely performed during stability studies and to optimize the freeze-drying process (lyophilization). Currently, Karl Fischer titration is widely used for moisture determination in routine analysis. However, this method is time consuming and destroys the sample during analysis. This Application Note shows that near-infrared spectroscopy (NIRS) is a fast, reagentless, non-destructive method to determine moisture content in lyophilized pharmaceutical products.

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

The separation of lactose, lactobionic acid, sialic acid*, 6’-sialyllactose, and 3’-sialyllactose is shown as a proof of concept for the control of these components in fermentation process for a pharmaceutical product. The acceptance criterion of a minimum resolution of the peaks (< 1.3) is reached. The separation is achieved on a Metrosep Carb 2 - 250/4.0 column with subsequent pulsed amperometric detection.

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.

This Application Note shows the rapid, non-destructive identification of isopropyl alcohol from two manufacturers using Raman spectroscopy following the creation of a suitable library. The measurements with the hand-held Raman spectrometer Mira M-1 require no sample preparation and provide immediate results that identify the samples unambiguously.

Material verification models with complex algorithms such as Principal Component Analysis (PCA), quasi-infinite parameters, and preprocessing options can be incredibly complex. Each model must be rigorously built, evaluated, and validated before it can be put into routine use. Mira P simplifies material verification for all. With a short, defined user workflow, straightforward results, and a foolproof Operating Procedure-based design, Mira P is already one of the simplest RMID tools available. ModelExpert, in Mira Cal P, does a chemometrician’s work. ModelExpert automatically determines the best model parameters for robust method development. With Mira P and ModelExpert, even non-technical users can achieve better results in a fraction of the time.

This Application Note explains how to scale MIRA P usage across an entire manufacturing operation by transferring models between different MIRA P instruments.

This application shows how to seamlessly transition from Metrohm’s NanoRam 785 to the newer MIRA P system, ensuring continuity in raw material identification (RMID).

Determination of sulfate in gentamicin sulfate using anion chromatography with conductivity detection after chemical suppression.

Determination of acetate and methanesulfonate (MSA) in olsalazine using anion chromatography with conductivity detection after chemical suppression.

Eltrombopag is a pharmaceutical agent used in certain conditions of thrombocytopenia. As such it is an orphan drug. The molecule of Eltrombopag is a protonated aromatic carboxyl compound. Under ion chromatography condition (alkaline eluent), it can be deprotonated and can thus block ion exchanger sites on the column. This results in decreasing retention times over time. To avoid this, Inline Matrix Elimination is applied, where the protonated Eltrombopag is washed off the preconcentration column before injection. Nitrite is then analyzed with conductivity detection after sequential suppression.

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.

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.

Ion chromatography (IC) with suppressed conductivity detection has been approved by the U.S. Pharmacopeia (USP) as a validated method to quantify the monofluorophosphate (MFP) content in sodium monofluorophosphate. This Application Note shows that all acceptance criteria for the USP Monograph «Sodium Monofluorophosphate» are fulfilled and the procedure was approved as a validated USP method.

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>.

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 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.