Analysis Of Residual Solvents Research Articles

Monitoring residual solvents in pharmaceutical products using a portable pre-concentration GC-PID

Pharmaceutical manufacturing utilizes solvents at different stages of production. Some of the harmful solvent residuals may be retained in the final product; therefore, they need to be monitored for quality control and to meet the regulation requirement. Here, a novel method capable of rapidly analyzing residual solvents in pharmaceutical products was developed using a compact-portable gas chromatography with a photoionization detector (GC-PID). The method consists of modified Tedlar® bag sampling, online pre-concentration, separation of volatiles by miniaturized GC, and micro-PID detection. The method detection limits of selected residual solvents were in the range of 26.00 – 52.03 pg/mL which is much lower than the pharmaceutical compliance concentration limits. Limits of detection > 520 pg of analyte per grams of sample was also determined for the over-the-counter drugs. The method performance showed rapid speed (5 min), linear calibration (r2 < 0.99), and repeatable retention time (RSD < 0.4 %). Direct analysis of residual solvents in solid samples was conducted without the need for complex sample preparation. The method validation using over-the-counter pharmaceutical products yielded excellent accuracy (recovery > 91.2 %) and precision (RSD < 6.5 %) for the selected residual solvents, including 1,4-dioxane, benzene, chlorobenzene, cyclohexane, xylenes, and toluene. This portable and rapid method could be deployed during the pharmaceutical drug manufacturing processes for quality control.

A novel Posaconazole oral formulation using spray dried solid dispersion technology: in-vitro and in-vivo study.

SD (solid dispersion) technology is one of the well-recognized solubility enhancement methods; but the use of versatile carriers in ASD (amorphous SD) to achieve the added advantage of modified release along with solubility improvement is an emerging area of exploration. Spray drying is a widely used technology with excellent scalability and product attributes. The SD carriers explored were Soluplus®, possessing excellent solubilization properties that may enhance bioavailability and is suitable for innovative processing, and Gelucire 43/01, a lipid polymer utilized in a non-effervescent-based floating gastro-retentive DDS for the modified release of API. The CPPs of spray drying were screened during preliminary trials, and the formulation variables were optimized using a 32 Full Factorial Design. All nine batches were evaluated for % yield, % drug content, flow properties, floating behavior, saturation solubility, and in-vitro drug release in 0.1 N HCl. The optimized batch characterized based on DSC (differential scanning calorimetry) and PXRD (powder X-ray diffraction) confirmed the amorphous nature of entrapped drug in SDD (spray-dried dispersion). Particle size analysis and SEM (scanning electron microscopy) demonstrated micron size irregular shaped particles. Residual solvent analysis by GCMS-HS confirmed the elimination of organic solvents from SDD. The optimized batch was found stable after 6months stability study as per ICH guidelines. In-vivo roentgenography study in New Zealand white rabbit showed the residence of SDD in gastric environment for sufficient time. The pharmacokinetic study was performed in male Sprague-Dawley rats to determine the bioavailability of developed SDD based product in fasting and fed conditions, and to compare the data with marketed Noxafil formulation. The current research is focused on the development of a novel ternary SDD (spray-dried dispersion)-based gastro-retentive formulation for an anti-fungal drug Posaconazole.

Extraction, identification and antitumor activity in cell cultures of cubebin isolated from dry seeds Piper cubeba (Piperaceae)

The Pipercubeba, it is one spice, widely consumed in Europe, which has several bioactive molecules, between those a lignan named cubebin. Cubebin has several known biological activities, such as analgesic activity and anti-inflammatory, trypanocidal activity, leishmanicidal and antitumor activity. The objective of this study was to evaluate the antiproliferative activity "in vitro" cubebin in eight different human tumor cell lines. It was fully characterized by IR analysis, NMR, mass spectrometry, DSC, TGA, residual solvent and elemental analysis. The antitumor activity of cubebin was evaluated "in vitro" on eight different human tumor cell lineages. Cubebin showed GI50≤30μg/mL for lineage cell U251 (glioma CNS), 786-0 (kidney), PC-3 (prostate), HT-29 (colon rectum). For K562 cells (leukemia), cubebin presented GI50≤to 4.0mg/mL. For the other lineages cells, MCF-7 (breast) and NCI-H460 to cubebin can be considered inactive because of GI50>250mg/mL. Analyzing the selectivity index for cubebin, it can be observed that high selectivity of cubebin to K562 lineage cells (leukemia). Analyzing the cytotoxic potential of cubebin was observed that probably acts cubebin altering metabolism, inhibiting cell growth-a cytostatic effect, showing no cytocidal effect on any lineage cell.

Pharmaceutical Residual Solvent Analysis: A Comparison of GC-FID and SIFT-MS Performance

Residual solvents in pharmaceutical excipients, active pharmaceutical ingredients (APIs), and finished products are usually analyzed using gas chromatography (GC)-based techniques according to a pharmacopeial monograph, such as the United States Pharmacopeia’s (USP) chapter &lt;467&gt;. GC analyses are often slow, which limits sample throughput. Selected ion flow tube mass spectrometry (SIFT-MS) removes the rate-limiting chromatographic separation step, potentially offering faster sample analyses. This approach was demonstrated recently with the publication of an alternative SIFT-MS procedure which was successfully validated against the performance criteria in USP chapter &lt;1467&gt;. The present study expands upon the previous work by conducting a head-to-head comparison of GC-flame ionization detection (GC-FID) and SIFT-MS procedures. The results obtained in this cross-platform study demonstrated similar performance for the GC-FID and SIFT-MS procedures for linearity (R2 &gt; 0.94 and 0.97, respectively) and repeatability (&lt;17%RSD and &lt;10%RSD). For accuracy and recovery, acceptance criteria (within 20%) were achieved for most compounds across the two drug products (SIFT-MS suffered fewer failures, possibly due to shorter wait times prior to analysis). Additionally, SIFT-MS analyzed samples over 11-fold faster than GC-FID, increasing daily sample throughput and reducing the time taken to determine the result. This study therefore suggests that residual solvent analysis using SIFT-MS may support workflow improvements for pharmaceutical manufacturers.

Clustering of Tadalafil API Samples According to their Manufacturer in the Context of API Falsification Detection

This paper reports the results of the active pharmaceutical ingredient (API) fingerprint study, organised by the General European Official Medicines Control Laboratory Network (GEON), on tadalafil. A classical market surveillance study, evaluating compliance to the European Pharmacopoeia, was combined with a fingerprint study, the latter to obtain characteristic data for the different manufacturers, allowing the network laboratories to conduct authenticity tests for future samples, as well as to detect substandard and falsified samples.In total, 46 tadalafil API samples from 13 different manufacturers were collected. For all samples fingerprint data was collected through analysis of impurities and residual solvents, mass spectrometric screening, X-ray powder diffraction and proton nuclear magnetic resonance (1H-NMR). Chemometric analysis revealed that all manufacturers could be characterised based on the impurity, residual solvent and 1H-NMR data. Future suspicious samples in the network will therefore be analysed with these techniques in order to attribute the sample to one of the manufacturers. If the sample cannot be attributed, a more profound investigation will be necessary to reveal the origin of the sample. In cases where the suspect sample is claimed to be from one of the manufacturers included in this study, analysis can be limited to the test distinguishing that manufacturer.

Microwave assisted vanillin crosslinked chitosan/polycarbophil superporous hydrogels for biomedical application: Optimization and characterization

Among the numerous macromolecules used in the formulation of superporous hydrogels, naturally occurring polysaccharides like chitosan, alginate, psyllium etc., offer better sustainable building blocks with improved characteristics. Present research work emphasis on development, optimization and characterization of novel superporous hydrogel containing microwave assisted vanillin crosslinked chitosan/polycarbophil (CVP). The preparation of CVP superporous hydrogels was systematically optimized using full factorial design. Optimized CVP superporous hydrogels were subjected for FTIR, DSC and XRD. Residual solvent analysis was performed by gas chromatography. Surface morphology was analysed using SEM. Optimized CVP superporous hydrogel showed good swelling in a pH ranging from 1 to 8 and can be prepared in desired shape and size. FTIR studies revealed the presence of desirable interactions between the polymers. DSC thermograms exhibited differences in comparison to individual polymer thermograms. Residual solvent analysis by gas chromatography method revealed concentration of acetone, in formulation was within permissible limits as per the ICH guidelines. SEM images clearly revealed the formation of the interconnected pores and capillary channels throughout out the formulation. Overall, the current study signifies that the optimized CVP superporous hydrogel formulation can be successfully formulated and employed for regulated delivery of drugs to the GI tract, buccal cavity, colon, vaginal, and rectal region for both local and systemic action for varied therapeutic purposes because of its ability to swell faster in wide range of pH.

Study on drug substance degradation under headspace GC conditions of residual solvent analysis.

Isobutyraldehyde (IBA) was detected in drug substance (DS) containing an amino acid group using a headspace-gas chromatography (HS-GC) method. High-performance liquid chromatography-mass-spectrometry (HPLC-MS) data from an HS vial confirmed that IBA was a degradant. The HS-GC method was modified to minimize IBA by keeping the HS oven temperature lower than 80 °C.

Analysis of Residual Solvents-Impurities by HS-GC-FID: Case of Seven Samples of Ciprofloxacin API.

Residual solvents are organic volatile impurities that can occur in the manufacture of Active Pharmaceutical Ingredients (APIs). Residual solvents analysis in pharmaceutical products is necessary not only because of they represent a potential risk for human health due to their toxicity and their undesirables side effects, but also because they may affect the physicochemical proprieties of pharmaceutical product. The main objective of this work was to analysis 29 residual solvents-impurities by Head Space Gas Chromatography with Flame Ionization Detector (HS-GC-FID) in seven samples of Ciprofloxacin Hydrochloride API, collected from seven pharmaceutical industries installed in Algeria. The GC was equipped with a flame-ionization detector and silica column coated with 1.8 µm layer of phase G43. The carrier gas was helium with a linear velocity of 35 cm/s and a split ratio of 1:5. The column temperature was 40 °C then it rised to 240 °C. The injection temperature was 140 °C and that of detector was 250 °C. Twenty-nine organic solvents belong to classes 1 and 2 were analyzed in seven samples of Ciprofloxacin Hydrochloride API whose control is mandatory because of their carcinogenic and intrinsic toxicity. Only five solvents were identified wich are Hexane, Toluene, Acetonitrile, Methanol and Dichloromethane in the different samples. All samples collected satisfied the test of identification, so, the confirmation and the quantification procedures weren’t realized. The HS-GC-FID technique used showed that the identified solvents differ from one sample to another of the same molecule. This showed that manufacturers didn’t often use the same solvents to produce the same API, which justifies that residual organic solvent tests weren’t usually mentioned in the specific monographs.

Development of surface modified nanoparticles of curcumin for topical treatment of diabetic retinopathy: In vitro, ex vivo and in vivo investigation

Diabetic retinopathy (DR) is the worst microvascular complication of diabetes that results in blindness. Present treatment of DR is invasive and associated with pain and inflammation. There is a need to develop painless treatment. The surface-modified PLGA (50:50) nanoparticles of Curcumin, which is a peroxisome proliferator-activated receptor-gamma agonist, were prepared to target DR by topical administration. Nanoparticles were optimized by a 32 factorial design. The Concentration of PLGA and number of HPH cycles at fixed pressure were independent variables whereas particle size. PDI and % entrapment efficiency were the dependent variables. Batch F6 with particle size, PDI, and % EE 194.7 nm, 0.231, and 90% respectively was selected as the optimized batch. The optimized batch was further subjected to spray drying and evaluated for various parameters. Residual solvent analysis was carried out by Gas chromatography. In vitro drug release study showed a biphasic drug release pattern of 70.17 ± 1.38% cumulative drug release at the end of 10 h. The release profile of curcumin from nanoparticles appeared to fit best with the Higuchi model. XRD study confirmed the molecular dispersion of the drug. The formulation showed satisfactory results in sterility testing, histology and isotonicity testing. In vivo study on rats showed dose dependent reduction in vascular endothelial growth factor (VEGF) concentration in vitreous fluid. Based on available evidences it can be concluded that the prepared formulation possesses great potential to manage diabetic retinopathy.

Method Development and Validation for Quantification of Residual Solvents in Atorvastatin Calcium Drug Substance by GC-HS Using Fid Detector

A proficient GC-HS method was developed for quantification of THIRTEEN residual solvents in Atorvastatin Calcium drugs substance with flame ionization detector (FID) using column Rtx-624, (60m length X 0.25mm diameter) 1.4µm film thickness, Part No.: 10969, Make: Restek. Nitrogen is used as Carrier gas with Linear velocity of 27.7cm/se on Shimadzu /GC-2010 Plus/HS-20 instrument. The proposed method was validated for System suitability, Specificity, Linearity, LOD and LOQ determination, Recovery, Precision, Range and Robustness. All the parameters were found within the acceptable limits. Linearity of all thirteen residual solvents are in the range of LOQ to 150%. The established methodology was commercially useful, specific, accurate, precise and suitable for the analysis of Residual solvents in Atorvastatin Calcium drug substance.

Application of Gas Chromatography for the Analysis of Residual Solvents in Transdermal Drug Delivery Systems (TDS)

Background: Transdermal drug delivery systems (TDS) are widely used to deliver a number of different drug therapeutics. The design delivery can be impacted by excipients and, more broadly, organic solvents. Organic or residual solvents are routinely monitored due to safety concerns. However, there is little information on the mechanical properties and delivery performance of TDS. Objective: The objective of this study was to develop and validate an efficient GC-Headspace method to determine the residual solvents (n-heptane, o-xylene, and ethyl acetate) in transdermal patches. The analytical method was applied to monitor residual solvents in TDS and evaluate the potential effect of the residual solvent levels on the TDS adhesion properties. Methods: An Agilent GC 7890A was integrated with an Agilent headspace analyzer 7697A system and was used for method development, analytical method validation, and the testing phases of the study. For the analysis of residual solvents in TDS, 2cm x 3cm, a TDS sample was placed in a 20 mL Headspace vial containing 2 mL of a DMSO/water (1:1, v/v) solvent mixture, and an external standard (cyclohexane) was extracted by the headspace analyzer. The system suitability test was conducted according to USP &lt;621&gt;, and analytical method validation was conducted according to USP &lt;1225&gt; over 3 days for validation and was also performed during in-study sample analysis. Results: The resolution between the solvents was acceptable (2.5, %RSD = 8.0). Intra- and inter- day accuracy and precision of all quality control standards as well as the spiked standards in the transdermal patches were found to be acceptable with RSD% ≤ 10% and accuracy ≥ 85%, respectively. Linearity was &gt; 0.99 for all analytes. Conclusion: The validated GC-Headspace method was successfully applied to a pilot study for in-house manufactured TDS patches to study the impact of residual solvent concentration on adhesion performance.

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&gt;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.

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 &amp; 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&gt;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.

Detection of Residual Solvents in Commercial Supplements Using Headspace (HS)-GC-MS

In order to understand the actual state of residual solvents contained in commercial supplements, we performed a simultaneous analysis of residual solvents by headspace (HS)-GC-MS with reference to the Japanese Pharmacopoeia's "Residual Solvents", for 29 products selected from among commercial supplements (e.g., revitalizers, weight loss pills) that are deeply colored or contain coating agents and extract powder. As a result, benzene (class 1) was detected in eight black-colored supplements, and hexane (class 2B) was also detected in one of those products. On the other hand, methanol (class 2A) was detected in four products containing coating agents and extract powders, such as citrus peel extract. None of these residual solvents exceeded the concentration limits set by the Japanese Pharmacopoeia. Benzene was detected at 1.7 μg/g, which was near the concentration limit, in some products. As raw materials used for the manufacture of the black-colored supplements from which benzene was detected commonly included activated carbon, we analyzed the residual solvents contained in activated carbon commercially available for use as food additive and in food production and medicine. As a result, benzene was detected at high concentrations in activated carbon made from hemp (approximately 29 μg/g) and bamboo (approximately 140 μg/g).

Nanoparticle-eluting stents for coronary intervention: formulation, characterization, and in vitro evaluation.

Coronary artery disease (CAD) is currently a leading cause of death worldwide. In the history of percutaneous coronary intervention for the treatment of CAD, a drug-eluting stent (DES) is recognized as a revolutionary technology that has the unique ability to significantly reduce restenosis and provide both mechanical and biological solutions simultaneously to the target lesion. The aim of the research work was to design and fabricate DES coated with a nanoparticulate drug formulation. Sirolimus, an inhibitor of the smooth muscle cell (SMC) proliferation and migration, was encapsulated in polymeric nanoparticles (NPs). The NP formulation was characterized for various physicochemical parameters. Cell viability and cell uptake studies were performed using human coronary artery smooth muscle cells (HCASMCs). The developed NP formulation showed enhanced efficacy compared to plain drug solution and exhibited time-dependent uptake into the HCASMCs. The developed NP formulation was coated on the Flexinnium™ ultra-thin cobalt-chromium alloy coronary stent platform. The NP-coated stents were characterized for morphology and residual solvent analysis. In vitro drug release was also evaluated. Ex vivo arterial permeation was carried out to evaluate the NP uptake from the surface of the stents. The characterization studies together corroborated that the developed NP coated stent can be a promising replacement of the current DESs.

Detection and Analysis of Residual Solvent in Drugs by Gas Chromatography

Detection and Analysis of Residual Solvent in Drugs by Gas Chromatography

A Review on – Estimation of Residual Solvents by Different Analytical Method

Residual solvents are the unwanted substances (solvents) used or created throughout the manufacture of a excipients, drug or pharmaceutical formulation and don't seem to be utterly removed by sensible ways within the final finished product. These solvents may be harmful in nature. Therefore, analysis of residual solvents becomes a necessary tool for the standard management of prescribed drugs. The appropriate limits for these substances are given in ICH. Solvents are widely used during the manufacturing, purification and processing of pharmaceutical substances. The residues of these solvents must be removed to the extent possible, as they do not have any therapeutic effect but can cause undesirable effects in the consumers. These solvent residues concentrationshould not exceed the limits prescribed in the ICH guidelines. This present review work is emphasized on various techniques (Loss on drying, Thermogravimetric analysis, Near- IR spectroscopy).

Residual solvent analysis with hyper-fast gas chromatography-mass spectrometry and a liquid carbon dioxide cryofocusing in less than 90 s

A new hyper-fast gas chromatography method with less than 90 s runtime including the column cool down was developed for the analysis of four gases and 16 residual solvents, combining a CO2 cryofocusing with a flow-field thermal gradient gas chromatograph (FF-TG-GC) and ToF-MS. The extremely low analysis time can be achieved by combining the new FF-TG-GC and a very short Rxi-624 Sil MS separation column with a small inner diameter and small film thickness (2.05 m × 0.1 mm × 1.0 µm).The column is inserted into a low thermal mass, resistively heated stainless steel capillary. This enables fast temperature programs with heating rates up to 3000 °C/min and a column cool down within a few seconds. In addition to temporal temperature gradients, the FF-TG-GC can generate a spatial temperature gradient that leads to an improved peak shape. Further, an external liquid CO2 cryo-trap was designed in order to reduce the injection bandwidths of analytes and to take full advantage of the resolving power of the separation column. No modifications are required to the FF-TG-GC for the use of the cryogenic trap, as the cooled spot is heated by the resistively heated stainless steel capillary during the temperature program. With cryofocusing, analyzed residual solvents are baseline separated. R2 values over 0.99 for calibration curves and low relative standard deviations (mainly < 3%) for repeatability tests were obtained.

Simultaneous Determination of Nine Residual Solvents in Sorafenib Tosylate by Gas Chromatography.

Direct injection gas chromatography is convenient and quick. The residual solvent with a higher boiling point can be measured by using direct inhection gas chromatography. This method could be developed for residual solvents analysis of sorafenible tosylate. In the present investigation, the injection method was developed and validated for the detection and quantification of residual solvents in sorafenib tosylate. The nine kinds of residual solvents were separated using direct injection gas chromatographic technology, and a quantitative analysis was performed. Analytical performance of the proposed injection method was validated as per the defined guidelines with respect to linearity, accuracy, precision, robustness, and specificity. Under the optimized conditions, simultaneous separation and determination of nine kinds of residual solvents, including methanol, acetonitrile, ethyl acetate, tetrahydrofuran, chlorobenzene, toluene, acetone, dichloromethane, and N, N-dimethylformamide were carried out using a DB-WAXETR polyethylene glycol Inertap Pure-WAX column (30 m × 0. 32 mm × 0.25 µm) for separation. The calibration plot was found to be linear, accurate, precise, robust, and specific for direct injection gas chromatography. The residual solvents in sorafenib tosylate were quantified by the developed method. The present method was successfully applied for analysis of residual solvents in sorafenib tosylate. Similarly, the method can be used for quality control and stability testing of other medicines. A validated GC assay for the combined analysis of the nine solutions which offered a reference method for the detection of residual solvents in other medicines.

Method development and validation for the determination of residual solvents in quinabut API by using gas chromatography. Message 2

Aim. The aim of study was to develop and validate a simple, precise and accurate method using gas chromatography for analysis of residual solvents – acetone and 2-propanol – in quinabut API. Materials and methods. All experiments were performed on a gas chromatographic system equipped with FID detector (Shimadzu GC System) using the DB-624 (30 m × 0.32 mm ID, 3.0 μm film sickness) column as stationary phase. Nitrogen was used as carrier gas with flow rate 7.5 mL/ min. Split ratio was 1:5, injector temperature was 140 °C, detector temperature was 250 °C, oven temperature was programmed from 40 °C (2 min) to 50 °C at 1 °C/min and then increased at a rate of 15 °C/min up to 215 °C; and maintained for 2 min. All solutions were prepared using water as diluent. Results. This proposed method is assessed for separation of residual solvent from quinabut with quantification. The obtained results are compared with the corresponding specified limits of ICH standard guidelines. The method validation was done by evaluating specificity, limit of detection (LOD) and limit of quantitation (LOQ), linearity, accuracy, repeatability, ruggedness, system suitability and method precision of residual solvents as indicated in the ICH harmonized tripartite guideline. The separation between acetone and 2-propanol peaks is 2.07. Hence method was found to be specific. The linear relationship evaluated across range of 15 to 180% for acetone and 2-propanol of ICH specified limit of residual solvents. The graphs of theoretical concentration versus obtained concentration are linear and the regression coefficients ‘R’ for residual solvents were more than 0.9968. The values of LOD and LOQ were much less than the lower limit of the concentration range and cannot affect the accuracy of the test. The technique was characterized by high intra-laboratory accuracy at concentrations close to the nominal acetone and 2-propanol concentration. All solutions were stable in water for at least 1 hour when stored at room temperature. Conclusion. A simple, specific, accurate, precise and rugged gas chromatography method was developed and validated for the quantification of residual solvents present in quinabut API through an understanding of the synthetic process, nature of solvents and nature of stationary phases of columns. The residual solvents acetone and 2-propanol were determined.