Headspace Gas Chromatographic Method Research Articles

Greenhouse Gas Emissions Characteristics and Driving Factors Analysis in the Eutrophic Saline Lake Daihai Lake

To investigate the greenhouse gas emission characteristics and driving factors of eutrophic saline lakes in northern China, considering Daihai Lake in Inner Mongolia as an example, 10 monitoring sites were selected based on hydrological distribution characteristics in April, July, and October 2023. Using headspace gas chromatography and modeling methods, dissolved concentrations and exchange fluxes of carbon dioxide （CO2）, methane （CH4）, and nitrous oxide （N2O） were determined in the nearshore zone, open lake area, and lake center surface water. During the study period, Daihai Lake exhibited significant seasonal variations in greenhouse gas concentration and flux. The average concentrations of CO2, CH4, and N2O in surface water were （26.52 ± 17.58） μmol·L-1, （282.30 ± 172.30） nmol·L-1, and （9.09 ± 1.64） nmol·L-1, respectively. The average fluxes were （5.29 ± 11.98） mmol·（m2·d）-1, （178.24 ± 63.34） μmol·（m2·d）-1, and （-0.74 ± 1.28） μmol·（m2·d）-1, with cumulative emissions of 50 770.77, 543.52, -4.21 kg·km-2 and a global warming potential （expressed in CO2-equivalent） of 50 770.77, 15 218.49, -1 254.48 kg·km-2. Daihai Lake acted as a source of atmospheric CO2 and CH4 but a sink for N2O during the study period. Correlation and stepwise regression analyses revealed that pH and total dissolved solids （TDS） influenced CO2 concentration and flux, while the factors affecting CH4 were water temperature （WT）, water depth （WD）, wind speed （WS）, oxidation-reduction potential （ORP）, and total nitrogen （TN）. For N2O, the influencing factors were WT, WS, and TN. Additionally, Daihai Lake's eutrophication and salinity characteristics influenced the generation and emission of greenhouse gases. This study provides insights into the greenhouse gas dynamics and environmental factors in eutrophic saline lakes like Daihai Lake.

Deep eutectic solvents as green and sustainable diluents in headspace gas chromatography for the determination of trace level genotoxic impurities in pharmaceuticals

Genotoxic impurities (GTIs) are potential carcinogens that need to be controlled down to ppm or lower concentration levels in pharmaceuticals under strict regulations. The static headspace gas chromatography (HS-GC) coupled with electron capture detection (ECD) is an effective approach to monitor halogenated and nitroaromatic genotoxins. Deep eutectic solvents (DESs) possess tunable physico-chemical properties and low vapor pressure for HS-GC methods. In this study, zwitterionic and non-ionic DESs have been used for the first time to develop and validate a sensitive analytical method for the analysis of 24 genotoxins at sub-ppm concentrations. Compared to non-ionic diluents, zwitterionic DESs produced exceptional analytical performance and the betaine : 7 (1,4- butane diol) DES outperformed the betaine : 5 (1,4-butane diol) DES. Limits of detection (LOD) down to the 5-ppb concentration level were achieved in DESs. Wide linear ranges spanning over 5 orders of magnitude (0.005–100 µg g−1) were obtained for most analytes with exceptional sensitivities and high precision. The method accuracy and precision were validated using 3 commercially available drug substances and excellent recoveries were obtained. This study broadens the applicability of HS-GC in the determination of less volatile GTIs by establishing DESs as viable diluent substitutes for organic solvents in routine pharmaceutical analysis.

A Static Headspace Gas Chromatography Method for Quantitation of Residual Solvents in Nanoformulations.

Various organic solvents are widely used in the manufacturing, processing, and purification of drug substances, drug products, formulations, excipients, etc. These solvents must be removed to the lowest amount permitted, as they do not possess any therapeutic advantages and may cause undesirable toxicities. Therefore, a rapid and sensitive analytical method for the quantitation of residual solvents is needed. The following chapter presents a static headspace gas chromatographic (HSGC) method for determining the concentration of common residual solvents in various nanoformulations. An efficient and sensitive HSGC method has been developed using PerkinElmer's headspace autosampler/gas chromatographic system with a flame ionization detector (FID) and validated according to the International Conference for Harmonization (ICH) guideline Q3C. The method validation indicates that the method is specific, linear, accurate, precise, and sensitive for the analyzed solvents. The method is suitable for the analysis of 13 residual solvents (methanol, ethanol, acetone, diethyl ether, 2-propanol, acetonitrile, 1-propanol, ethyl acetate, tetrahydrofuran, dichloromethane, chloroform, 1-butanol, and pyridine) and utilizes an Elite 624 Crossbond 6% cyanopropylphenyl, 94% dimethylpolysiloxanes column with helium as a carrier gas.

DEVELOPMENT AND VALIDATION OF THE HS-GC-FID METHOD FOR THE QUANTIFICATION OF RESIDUAL SOLVENTS IN DESLORATADINE

Testing for residual solvents is a crucial component of both reference material certification and pharmaceutical quality control. Developing and validating a head space-gas chromatography method for measuring residual solvents in desloratadine in pharmaceutical dosage forms was the aim of the current investigation. To create desloratadine, an active ingredient in pharmaceuticals, the pharmaceutical industry commonly uses organic solvents such as methanol, diethyl ether, dichloromethane, and tetrahydrofuran. A novel technique for measuring residual solvents in desloratadine was created using a flame ionization detector and headspace gas chromatography. HP1 Column (30m×0.53mm, 1.8µm), intake port maintained at 250°C, detector temperature 260°C, oven temperature 190°C, and injection volume 1µl with 1:50 split ratio utilizing nitrogen as a carrier gas at a flow rate of 1ml/min were the optimum chromatographic conditions. Using criteria from the International Conference on Harmonization, the method's linearity, range, detection limit, quantitation limit, accuracy, precision, specificity, system appropriateness, and robustness were all validated. It was determined that the idea was appropriate for determining four distinct residual solvents. The approach is particular, linear, exact, accurate, and sensitive, according to validation data, where recoveries varied from 90 to 110 percent. This thoroughly tested technique has been used to identify any remaining solvents in actual desloratadine bulk samples.

Determination of four residual solvents in cefepime by headspace gas chromatography

ObjectiveTo establish a headspace gas chromatography method to determine the residual solvents of methanol, acetone, dichloromethane, and toluene in cefepime. MethodsHeadspace gas chromatography using a DB-624 capillary column and temperature program was performed to detect four residual solvents in cefepime. The temperature program consisted of an initial temperature of 60 ℃maintained for 4 min, a temperature increased to 120 ℃ at 20 ℃·min−1 maintained for 3 min, and then a temperature increased to 200 ℃ at 40 ℃·min−1 maintained for 3 min. ResultsLinear relationships were found between the peak areas and mass concentrations of the four solvents mentioned above within the defined ranges. The limits of detection for methanol, acetone, dichloromethane and toluene were 0.50, 0.15, 0.10 and 0.08 mg·L-1, respectively. The recoveries obtained using the standard addition method ranged from 98.41 % to 100.94 %. ConclusionThis method demonstrated high sensitivity and good reproducibility, and it can be used to effectively control the residual amounts of methanol, acetone, dichloromethane, and toluene, to further improve the quality of cefepime.

Degradation Mechanism Study for Secondary Degradants in Rosuvastatin Calcium and Determination of Degradant Acetaldehyde Using Static Headspace Gas Chromatography Coupled with Matrix Precipitation

During the development of headspace gas chromatography (HSGC) method for assessing residual solvents in rosuvastatin calcium (RSV) drug substance, acetaldehyde (AA) was detected in obtained chromatograms, with a calculated concentration of up to 226 ppm. After a series of experiments, it was established that acetaldehyde originates from matrix interference due to direct degradation of Imp-C, which is accompanied by the formation of impurity at relative retention time (RRT) 2.18, without the involvement of impurity at RRT 2.31. The thermal instability of Imp-C also results in the formation of impurity at RRT 2.31 through dehydration and decarboxylation. In addition, cyclization reaction of degradant at RRT 2.18 further resulted in the generation of impurity at RRT 2.22. The structure of these three degradants, were confirmed by liquid chromatography-mass spectrometry (LC-MS), 1D and 2D nuclear magnetic resonance (NMR) measurement. In order to minimize the said matrix interference, a simple precipitation procedure was proposed as a pretreatment to mitigate the impact of Imp-C. Subsequently, an HSGC method was developed for the simultaneous determination of the degradant AA and the other five residual solvents used in RSV synthetic process. The final method was validated concerning precision, limit of detection (LOD) and limit of quantitation (LOQ), linearity, and accuracy.

Development and Validation of Headspace-Gas Chromatography (HS-GC) Method for the Determination of Potential Genotoxic Impurities in Meloxicam

The development and validation of a specific Headspace-Gas Chromatography (HS-GC) method for the determination of genotoxic impurities (isopropyl chloride, propionaldehyde, 2-chloropropanol, and chloromethane) in Meloxicam. The chromatographic separation of these impurities was accomplished using a nitrogen carrier gas on a DB-624 (6% cyanopropyl phenyl + 94% dimethyl polysiloxane fused silica) (75 m x 0.53 mm, 3.0 µ) GC analytical column. The Flame Ionization Detector (FID) served as the detector with optimized temperatures set at 260°C for the detector and 240°C for the injector port. Additionally, an injection volume of 1.0 mL with a split ratio mode was employed. The performance of this method was assessed through parameters, including system suitability, specificity, linearity, range, accuracy, limit of detection (LOD), limit of quantification (LOQ) and precision. The limit of detection and limit of quantification for isopropyl chloride, propionaldehyde, 2-chloropropanol, and chloromethane were determined to be 2 and 4 ppm, respectively, and for chloromethane 0.8 and 1.6 respectively. The correlation coefficient of the linearity experiment was 0.999 for propionaldehyde, 2-chloropropanol, chloromethane and 1 for isopropyl chloride compounds. Furthermore, the accuracy assessment involved spiking the genotoxic impurities at various levels, demonstrating favourable recovery percentages well within the acceptable range of 80–120% of the limit level. These compelling results substantiate the suitability of the proposed HS-GC method for the accurate determination of isopropyl chloride, propionaldehyde, 2-chloropropanol, and chloromethane in Meloxicam.

Platform headspace gas chromatography method for high-throughput determination of residual solvents in pharmaceutical materials

Static headspace capillary gas chromatography (HSGC) has been employed to monitor the level of residual solvents in the pharmaceutical materials. Most of the HSGC methods, however, consume significant amounts of diluents and require considerable amount of sample preparation time. Accordingly, a HSGC method featured with fast turnaround time, and minimal amount of solvent use has been developed for the quantitative analysis of 27 residual solvents frequently used in the development and manufacturing processes of pharmaceutical industry. This HSGC-FID method employs a commercially available fused silica capillary column, a split injection (40:1), and a programmed temperature ramp. It was qualified for specificity, accuracy, repeatability/precision, linearity, LOQ, solution stability, and robustness using two representative sample matrices. The standards, samples and spiked samples were demonstrated to be stable for at least 10 days at room temperature in sealed headspace vials with a recovery of ≥ 93%. The method was also shown to be robust, and its performance was not affected by small changes of carrier gas flow rate, initial oven temperature or the headspace oven temperature. In this new approach, the analytical sample was prepared by dissolving the sample into 1 mL of the diluent and the standard solution was prepared by diluting 1 mL of the custom-made stock into 9 mL of the diluent whereas the traditional approach requires liters of the diluent, making the new approach environmentally friendly, sustainable, economical, agile, error-proofing and thus appropriate for a variety of pharmaceutical applications.

Development and validation of determination of genotoxic impurity Bromoethane in Vigabatrin drug substance using head space gas chromatographic method [HS-GC

A specific HS-GC method has been developed, optimized, and validated for the determination of genotoxic impurity Bromoethane in Vigabatrin (VGB) drug substance. Chromatographic separation of genotoxic Bromoethane impurity was achieved on DB-1 column (30 m × 0.53 mm, 5.0 μm), consists of 100% dimethyl polysiloxane as stationary phase and passing nitrogen carrier gas. The performance of the method was assessed by evaluating the specificity, linearity, sensitivity, precision, and accuracy experiments. The established limit of detection and limit of quantification values for the genotoxic impurity was in the range of 3.57–10.80 μg/mL. The correlation coefficient value of the linearity experiment was 0.9880. The average recoveries for the accuracy were in the range of 95.3–106.8%. The results proved that the method is suitable for the determination of Bromoethane content in Vigabatrin.

Estimation of silage VOC emission impacts of surface-applied additives by GC-MS

Ensiling, the process of microbial acidification and preservation of wet forage for livestock feed that yields silage, produces a significant amount of volatile organic compounds (VOCs). Measurement of the chemical species involved, their emission to the atmosphere, environmental impacts, and economic losses to agricultural producers have been discussed in previous studies. Strategies for mitigation of silage VOC emission are limited and focus primarily on ensiling efficiency and silage additives at time of ensiling. However, one novel strategy employed by some producers to reduce airborne particulates, “wetting down” or applying water to rations at the feed bunk may also impact VOCs emission. We tested this method in parallel with several other chemical solutions with potential nutritional relevance for effects on VOC emission from silage. A headspace gas chromatography (GC) method was adapted for use with a paired mass spectrometer (MS) to profile silage. The effects on corn silage VOC emissions of surface-applied solutions across a range of pH, viscosity, and hydrophobicity were determined by GC-MS VOC headspace measurements. Surface-applied liquid additives included: water, citric acid, malic acid, molasses, sorghum syrup, yucca extract, seaweed extract, vegetable glycerine, olive oil, grape seed oil, and sunflower oil. Sample-to-sample variation among vials containing 5 g fresh weight (fw) silage collected from a bulked, homogenized silo sample was high, highlighting a need for sufficient replication. The most prevalent volatile acid in corn silage, acetic acid, made up the majority of observed VOCs. However, in total, eighteen VOCs were detected across all samples and the effects of treatments were assessed for each individually and for their sum as total VOC emission. Water applied to the surface of silage samples did not significantly alter VOC emissions as compared to silage alone for most VOCs. The largest observed significant effects were from the oil additives. Grape seed oil increased acetaldehyde and acetone values, while sunflower seed oil increased propionic acid and propyl acetate. Several treatments, including vegetable glycerine and seaweed extract, led to numerical decreases in VOC emissions and lower emission variability. More work is needed to understand interactions between silage VOC emissions and surface-applied mitigation strategies, including: constraining silage sample heterogeneity; investigation of the prevalence of oil-based feed additives and potential impacts on whole-farm VOC emissions; and in situ, on-farm measurements of VOC emission from treated piles.

알루미늄 포스파이드 중독 사망 사례

Aluminum phosphide is a fumigant used to kill insects or other animals in stored grains. We report a suicidal case using aluminum phosphide and phosphine gas was detected in the post-mortem specimen. Headspace gas chromatographic method with mass detector(HS-GS/MS) was used to detect phosphine from the gastric contents and the scene evidence.

Full evaporation headspace technique with gas chromatography as a microchemical method for the rapid determination of gamma-hydroxybutyric acid (GHB) in serum samples

The misuse of GHB as a knockout agent continues to increase. A full evaporation technique with headspace gas chromatography and flame ionization detection (FET-HS-GC-FID) method has been developed for the rapid determination of GHB (gamma-hydroxybutyric acid; “liquid ecstasy”) in serum samples. GHB occurs as an endogenous substance in low concentrations in mammals, is used as a recreational drug and misused as an agent in drug-facilitated sexual assaults or robbery as “knock out drops” in higher concentrations. Rapid determination of substances is particularly important in emergency analysis, especially in the case of unconscious patients.The FET-HS-GC-FID method developed in this paper operates with a sample volume of only 8 µL serum and provides slightly better validation data than the comparison method, which works with 200 µL serum. In order to be able to detect the low-volatile GHB, this is in situ converted into the high volatile lactone under acidic conditions. A thermostatting time of 20 min at 130 °C is sufficient for the lactonization.The FET-HS-GC-FID method enables the detection of GHB to GBL (gamma-butyrolactone) with a limit of detection (LOD) of 1.25 mg L−1, and a limit of quantification (LOQ) of 4.26 mg L−1 in serum samples. The method shows a good precision intraday (7.2 and 6.4 %) and interday (7.8 and 5.6 %) for both the low (lQC) and the high quality control (hQC) sample and a calibration curve determination coefficient (R2) of 0.999.The comparison of 100 spiked serum samples with GHB show an excellent agreement between the conventional and the new developed FET-HS-GC-FID method with a R2 of 0.984 and the results of the proficiency tests showed a very good agreement with the target values and were in all cases within the assessment limits.

Development and Validation of Head-Space Gas Chromatographic Method in Tandem with Flame ionized detection for the determination of Residual Solvents in Letermovir API synthesis

Residual solvent testing is an integral part of reference material certification. A gas chromatography / flame ionization detector/headspace method has been developed and validated to detect and quantitate commonly used residual solvents in our production processes: ethyl acetate, MTBE, Toluene and isopropyl acetatein Letermovir API. HS-GC method in a simple and selective manner is delineated for the quantification and determination of Residual Solvents in Letermovir API. The separation of solvents along with drug on Chromatographic chamber was processed on USP G43 equivalent capillary column Thermo Scientific™ Trace GOLD™ TG-624 SilMS, 30 m × 0.32mm × 1.8µm column (P/N 26059-3390) using nitrogen as carrier gas by using different temperature gradient of FID Detectors. Linearity was observed in the range 10-50µg/ml for ethyl acetate, MTBE, Toluene and isopropyl acetate (r2>0.999) for the amount of solvent determined through sophisticated methods was in good agreement. The proposed methods were validated. The method of accuracy was assessed by recovery studies at three different levels.The method was found to be precise as indicated by the repeatability analysis, showing %RSD less than 10 for ethyl acetate, MTBE, Toluene and isopropyl acetate. All statistical data proves validity of the methods and can be used for routine analysis of pharmaceutical active ingredients for estimation of Residual Solvents of ethyl acetate, MTBE, Toluene and isopropyl acetate in Letermovir. Method validation comprised the following parameters: limit of detection (LOD), limit of quantitation (LOQ), linearity and range, accuracy, precision (repeatability and intermediate precision), system suitability, specificity, and robustness. Linearity (micrograms/mL) and LOQ (ppm) are listed for each solvent in manuscript. The present method was proven to be robust and accurate for quantitative analysis of residual solvent in neat materials.

Diffusive Fluxes and Controls of N2O from Coastal Rivers in Tianjin City

Rivers are an important emission source of greenhouse gases. To explore the spatial characteristics and influencing factors of N2O emission from the coastal rivers in Tianjin City, six rivers into the Bohai Sea from different land-use types were selected, and the N2O concentrations, saturation, and diffusive fluxes were measured using the headspace-gas chromatography method. The N2O concentration was in supersaturation, and the rivers were the source of atmospheric N2O. The average concentration, saturation, and diffusive fluxes of N2O were (23.85±15.20) nmol·L-1, (309.71±197.38)%, and (27.04±16.46) μmol·(m2·d)-1, with the ranges of 12.70-115.69 nmol·L-1, 164%-1502%, and 9.17-244.79 μmol·(m2·d)-1, respectively. The N2O concentrations and diffusive fluxes of the rivers presented great spatial heterogeneity, with the sewage river (Huangdipai River)>urban river (Haihe River main stream, Jiyun River)>suburban river (Duliujian River, Yongding Xinhe River)>agricultural river (Chaobai Xinhe River). The N2O concentration and diffusion fluxes were significantly correlated with salinity, nutrients, and carbon sources. NO3--N and TP contributed greatly to the diffusive flux differences. N2O production and emission greatly related to the nitrogen cycle process in the Tianjin River, and different forms of nitrogen variously contributed to N2O diffusive fluxes. The salinity gradient had the opposite effect on the N2O emission in urban rivers and drainage rivers. The N2O diffusive fluxes of the sewage river in Tianjin were significantly higher than that of other river types. In the future, due to the development of urbanization and the expansion of urban land, more management measures should focus on the hotspots such as the downstream of wastewater treatment plants of sewage rivers, the estuaries of urban rivers, and the residential gathering areas of suburban rivers to reduce N2O emission.

Quantification of organic volatile impurities in Oseltamivir phosphate drug substances by head space gas chromatography

BackgroundThe present work is aimed at quantification of organic volatile solvents like Methanol, Ethanol, Acetonitrile, Isopropyl alcohol (IPA), Dichloromethane (DCM), Methyl tert-butyl ether (MTBE), Hexane fractions, Ethyl acetate (EA), Tetra hydro furan (THF), 1,4-Dioxane, Dimethylformamide (DMF), and Toluene in Oseltamivir phosphate Active pharmaceutical ingredient (API) and pharmaceutical dosage forms. The method was developed using a thermal gradient elution program associated with a column having dimensions are DB-1,60 m × 0.32 mm × 5.0 μm with a flow rate of 1.0 mL/min and Nitrogen (N2) as a carrier gas. A flame ionization detector was used as a detector, and its temperature is at 290 °C whereas the injector temperature is at 180 °C. The total run time is 60.0 min. The developed method was validated according to International Council for Harmonization (ICH) guidelines.ResultsThe linearity of the calibration curve for twelve impurities in the concentration range of Limit of Quantification (LOQ) to 150% was good. The curve was linear for twelve residual impurities of Oseltamivir phosphate. Relative standard deviation values for twelve residual impurities are not more than 15%. Limit of detection (LOD) and LOQ for twelve residual impurities were found to be very low-level concerning specification level. We found good results for all validated parameters for twelve residual impurities.ConclusionsTo quantify the residual organic volatile solvents (organic volatile impurities) in the Oseltamivir phosphate API, a novel, specific, and elevated sensitive headspace gas chromatography method was developed to separate twelve solvents that are accompanying with fifteen peaks. Out of fifteen peaks, critical components are Hexane fractions, Ethyl acetate, MTBE, and DCM. So, our method has capable of separating and simultaneous quantification such critical components. So, it can be successfully applied for routine analysis of quantification of these twelve residual impurities in Oseltamivir phosphate bulk and pharmaceutical dosage forms.

Determination of methanol partition coefficient in octanol/water system by a three-phase ratio variation headspace gas chromatographic method

Determining the methanol partition coefficient (Kow) in octanol/water system is important to assess the risk of its impact to humans and the environment. In this paper, we report a novel method for the determination of the Kow of methanol with headspace gas chromatography (HS-GC), using a three-phase equilibrium-based phase ratio variation approach. Three headspace vials with different phase ratios [(1) 0.2mL of water plus 3mL of octanol, (2) 1mL of water plus 3mL of octanol and (3) 1mL of water plus 10mL of octanol] were used in the experiment. After pre-standing at 25 °C for > 10h and equilibrating in the headspace oven at a temperature of interest for additional 25min, the methanol signals of the vapor phase (i.e., the headspace) in these vials were measured by HS-GC, from which the Kow of methanol can be calculated based on the established equations. The results showed that the method has good precision (within 0.06 log unit in standard deviation) and acceptable accuracy (with method error within 0.5 log unit). A correlation between the Kow of methanol and temperature extrapolated the Kow values in a temperature range of interest. The present method represents a simple and in-situ approach for the determination of the Kow of methanol and is also suitable to be applied to other volatile compounds.

A Full Evaporation Static Headspace Gas Chromatography Method with Nitrogen Phosphorous Detection for Ultrasensitive Analysis of Semi-volatile Nitrosamines in Pharmaceutical Products

The recent detection of potent carcinogenic nitrosamine impurities in several human medicines has triggered product recalls and interrupted the supply of critical medications for hundreds of millions of patients, illuminating the need for increased testing of nitrosamines in pharmaceutical products. However, the development of analytical methods for nitrosamine detection is challenging due to high sensitivity requirements, complex matrices, and the large number and variety of samples requiring testing. Herein, we report an analytical method for the analysis of a common nitrosamine, N-nitrosodimethylamine (NDMA), in pharmaceutical products using full evaporation static headspace gas chromatography with nitrogen phosphorous detection (FE-SHSGC-NPD). This method is sensitive, specific, accurate, and precise and has the potential to serve as a universal method for testing all semi-volatile nitrosamines across different drug products. Through elimination of the detrimental headspace-liquid partition, a quantitation limit of 0.25 ppb is achieved for NDMA, a significant improvement upon traditional LC-MS methods. The extraction of nitrosamines directly from solid sample not only simplifies the sample preparation procedure but also enables the method to be used for different products as is or with minor modifications, as demonstrated by the analysis of NDMA in 10+ pharmaceutical products. The in situ nitrosation that is commonly observed in GC methods for nitrosamine analysis was completely inhibited by the addition of a small volume solvent containing pyrogallol, phosphoric acid, and isopropanol. Employing simple procedures and low-cost instrumentation, this method can be implemented in any analytical laboratory for routine nitrosamine analysis, ensuring patient safety and uninterrupted supply of critical medications.Graphical

QUANTITATIVE DETERMINATION OF RESIDUAL SOLVENTS IN PALONOSETRON API BY HS-GC METHOD

Objectives: Palonosetron is an antidote to 5-HT3 in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). The presence of residual solvents in pharmaceutical drug substances or products, as well as excipients, can have a detrimental effect on the product’s quality and stability. These substances must be evaluated for safety and efficacy. The primary purpose of this work is to establish a method for validating and quantifying residual solvents in palonosetron API using Head Space Gas Chromatography (HS-GC). Methods: In the proposed HS-GC technique for the quantifying residual solvents - ethanol, acetone, methanol, acetonitrile, and isopropyl alcohol (IPA) in Palonosetron API, the headspace equilibrium was achieved at 100°C and analyzed by DB-624 column (30 m × 0.24 mm, 1.8 μm) with injector and detector temperature set at 200°C and 230°C respectively. The dissolving solvent was dimethyl sulfoxide (DMSO). After the initial holding time of 5mins, the temperature was increased to 120°C from 40°C in 20mins at a rate of 10°C/min using a flow rate of 10 ml/min and a split ratio of 1:25 with nitrogen as carrier gas. The approach created has been validated and quantified as per International Conference on Harmonization’s (ICH) guidelines. Results: All the results obtained were within the ICH specified limits. The validation results for repeatability studies (%RSD values) were found to be <10; recovery studies values were in the range of 90–110% and for the selected linearity range 25–150 μg/ml the correlation coefficients(γ2) for all the solvents were observed to be >0.99. Conclusion: A sensitive, simple, precise, and economic HS-GC method with Flame Ionization Detector (FID) was developed and validated to quantitatively determine the residual solvents in Palonosetron API.

ESTIMATION OF RESIDUAL SOLVENTS IN NETUPITANT API BY HEADSPACE GAS CHROMATOGRAPHY

Objective: Residual solvents are undesirable components present in Active Pharmaceutical Ingredients (API), excipients, or drug products. To meet the specific quality-based requirements, the presence of these solvents in pharmaceutical products should be monitored to ensure their safety. The main objective of this work is to develop a new method for the determination of residual solvents in netupitant API by an HS-GC method with an FID detector. Methods: An automated headspace GC method has been developed and validated for the estimation of the residual solvents-N-methyl pyrrolidine, xylene, toluene, and N, N Dimethylacetamide in netupitant API. The samples were dissolved in dimethyl sulfoxide and the equilibrium headspace gas was formed at 80 ᵒC, which was analyzed using a DB-624 column (30m*0.53 mm, 3.00 µm) with an injector and detector temperature set at 160 ᵒC and 230 ᵒC, respectively. The initial oven temperature was set at 60 ᵒC for 5 min and programmed at a rate of 10 ᵒC/min to the final temperature of 150 ᵒC, with a hold time of 5 min by maintaining the flow rate of 4.0 ml/min with a split ratio of 1:10, and total run time of 20 min. Nitrogen was used as carrier gas. The method developed was validated as per International Conference for Harmonization (ICH) guidelines for repeatability, linearity, range, ruggedness, detection limit, quantification limit, and recovery studies. Results: The linearity range selected was 50-350µg/ml and the correlation coefficient(γ2) values for all the solvents were found to be>0.99; recovery studies values were in a range of 90-110% and %RSD values were also found to be not more than 10 for the solvents. Conclusion: A novel, accurate, sensitive, and simple method was described for estimating residual solvents in Netupitant API by Headspace Gas Chromatography (HS-GC) coupled with a Flame Ionization Detector (FID). Excellent results have been observed for all the validated parameters with good peak resolution and lesser retention times.

Development and Validation of Head-space Gas Chromatographic Method in Tandem with Flame ionized detection for the determination of Residual solvents in Simeprevir API Synthesis

Residual solvent testing is an integral part of reference material certification. A gas chromatography/flame ionization detector/headspace method has been developed and validated to detect and quantitate commonly used residual solvents in our production processes: Methanol, Tetrahydrofuran, Toluene, Dichloromethane and Dichloroethane in Simeprevir API. A simple and selective HS-GC method is described for the determination & quantification of Residual Solvents in Simeprevir API. Chromatographic separation was achieved on USP G43 equivalent capillary column Thermo Scientific™ Trace GOLD™ TG-624 SilMS, 30m × 0.32mm × 1.8µm column (P/N 26059-3390) using nitrogen as carrier gas by using different temperature gradient of FID Detectors. Linearity was observed in the range 40-120% of standard concentrations for Methanol, Tetrahydrofuran, Toluene, Dichloromethane and Dichloroethane (r2>0.999) for the amount of solvent estimated by the proposed methods was in good agreement. The proposed methods were validated. The accuracy of the methods was assessed by recovery studies at three different levels. Recovery experiments indicated the absence of interference from commonly encountered diluent and API. The method was found to be precise as indicated by the repeatability analysis, showing %RSD less than 10 for Methanol, Tetrahydrofuran, Toluene, Dichloromethane and Dichloroethane. All statistical data proves validity of the methods and can be used for routine analysis of pharmaceutical active ingredients for estimation of Residual Solvents of Methanol, Tetrahydrofuran, Toluene, Dichloromethane and Dichloroethane in Simeprevir. Baseline separation of all five solvents and Simeprevir API is achieved within 20.5 minutes of analysis time. Method validation comprised the following parameters: limit of detection (LOD), limit of quantitation (LOQ), linearity and range, accuracy, precision (repeatability and intermediate precision), system suitability, specificity, and robustness. Linearity and LOQ (ppm) are listed for each solvent in manuscript. The present method was proven to be robust and accurate for quantitative analysis of residual solvent in neat materials.