Analysis Of Residual Solvents Research Articles

Headspace gas chromatographic analysis of residual solvents in pharmaceuticals: comparison of two matrix media

Dimethylformamide (DMF) and a deep eutectic solvent choline chloride-ethylene glycol (ChCl-Eg) were investigated as potential matrix media for static headspace gas chromatographic (SHS-GC) determination of residual solvents in pharmaceuticals. Sample equilibration temperature, equilibration time and injection time were optimized. In the case of DMF 140°C equilibration temperature was applied. For ChCl-Eg equilibration temperature could not exceed 80°C as ChCl-Eg started to degrade at elevated temperatures. The higher equilibration temperature of DMF solutions favoured a transition of the analytes to the headspace and consequently resulted in lower detection limits of the analytes. Thus DMF has been considered a more suitable matrix medium than ChCl-Eg and was applied for the SHS-GC determination of residual solvents in pharmaceuticals.

Solubility Enhancement of Methotrexate by Solid Nanodispersion Approach for the Improved Treatment of Small Cell Lung Carcinoma.

The present work aimed to develop MT loaded solid Nano dispersion by improving its solubility, half-life and bioavailability in biological system thereby this formulation may be afforded economically. Small cell lung carcinoma is a type of malignant tumor characterized by uncontrolled cell growth at lung tissues. The potent anti-cancer drug methotrexate (MT) chosen for the present work is poorly soluble in water (BCS type IV class) with short half-life and hepatotoxic effect. With the concept of polymeric surfactant to improve the solubility along with wettability of drugs, the present work has been hypothesized to improve its solubility using polyvinyl pyrollidone (PVP K30) polymer and α- tocopheryl polyethylene glycol 1000 succinate (TPGS) surfactant, thereby the bioavailability is expected to get enhanced. By varying the PVP K30 and TPGS ratios different formulations were developed using emulsification process. The developed MT loaded solid nanodispersion was further characterized for its particle size, charge, morphology, encapsulation efficiency and in-vitro release behavior etc. Results: The results of FT-IR spectrometric analysis indicated the compatibility nature of MTX, PVPK30 and TPGS. The developed formulations showed spherical morphology, particle size ranging from 59.28±24.2 nm to 169.33±10.85 nm with a surface charge ranging from -10.33 ± 2.81mV to -9.57 ± 1.2 mV. The in vitro release studies as performed by dialysis bag method showed a sustained release pattern as checked by UV Spectrophotometer. Residual solvent analysis for MTXNDs performed by HPLC indicates there is no residual DMSO in the formulation. Transmission electron microscopic image of MTXNDs revealed that the particles are spherical shaped with a solid core structure. Haemolytic assay indicates that the developed formulation is safe for intravenous administration. Cell culture studies in A549 cells indicates the enhanced cytotoxic effect for the developed formulation. This proof of study indicates that the developed formulation may have anticancer potential for SCLC treatment.

Synthesis and characterization of high‐purity N,N‐dimethyltryptamine hemifumarate for human clinical trials

Since 2006, there has been a resurgent interest in the pharmacology and therapeutics of psychedelic drugs. Psilocybin, the 4-phosphoryl ester of N,N-dimethyltryptamine (DMT), has been studied most often, but DMT itself is also appealing because of its brief but profound psychological effects and its presence as an endogenous substance in mammalian brain. Although there have been a few studies of ayahuasca, a DMT-containing water infusion, only one human study with pure DMT has been reported since the early 2000s. Newly planned clinical trials to assess the safety and efficacy of DMT in humans with major depressive disorders require high-purity water-soluble DMT for intravenous administration. Accordingly, we synthesized and characterized DMT hemifumarate for these upcoming studies. The synthetic approach of Speeter and Anthony was slightly modified to gain some efficiency in time. In particular, this is the first known report to use aluminum hydride, generated in situ from lithium aluminum hydride, to reduce the intermediate 2-(1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide to DMT. A quench protocol was developed to produce a good yield of exceptionally pure free base DMT upon workup, which was then converted to the hemifumarate salt. Analysis of the final product included differential scanning calorimetry, thermogravimetric analysis, gas chromatography-mass spectrometry (GC-MS), 1 H and 13 C nuclear magnetic resonance spectroscopy, high-performance liquid chromatography, residual solvent analysis by GC headspace sampling, X-ray powder diffraction analysis, and residual lithium analysis by inductively coupled plasma-mass spectrometry. The DMT hemifumarate was minimally 99.9% pure, with no significant impurities or residual solvents, thus meeting regulatory standards for administration to humans.

Headspace GC/MS Analysis of Residual Solvents in Dietary Supplements, Cosmetics, and Household Products Using Ethyl Lactate as a Dissolution Medium.

The static headspace technique is one of the most popular techniques for residual solvent analysis and dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF) are widely use as the dissolution media. This study aims to establish ethyl lactate (EL), a solvent with low toxicity and less environmental impact, as an alternative dissolution medium to DMSO and DMF for the static headspace analysis of toxic residual solvents in food, cosmetics, and similar complex organic matrices. Samples (a sample of dietary supplement and two samples each of cosmetics and household products) spiked with benzene, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethene, and 1,1,1-trichloroethane were dissolved in EL, DMSO, and DMF. Static headspace GC/MS and the standard addition method were used to detect and quantify the residual solvents. The dissolution and dispersion of these samples, especially the ones which were water-insoluble, were better than those in DMSO and DMF. The recoveries, except that of benzene in an aerosol spray, in EL ranged from 77 to 110%. The relative SDs in EL ranged from 2.5 to 11% and were better or equivalent to those in DMSO and DMF. EL was suitable as the dissolution medium for such samples, which may contain large amounts of organic solvents or various ingredients, in static headspace GC/MS analysis of residual solvents.

Development and validation of a thermal desorber gas chromatography method for determination of residual solvents in drug loaded albumin

The conventional approach for residual solvent (RS) analysis is headspace-gas chromatography (HS-GC). This starts from a homogenous sample solution and is based on the equilibrium of the analyte between the sample and the gas phase. Unfortunately, aqueous solutions of albumin form irreversible hydrophobic aggregates when heated above 50 °C. Consequently, the use of HS-GC for RS analysis in albumin becomes problematic due to the presence of an additional solid phase in the HS vial.In this work, a method using a thermal desorber (TD) combined with GC was developed for the determination of RS in drug loaded albumin. Samples were immobilized between two double layers of quartz filter (QF) in a polytetrafluoroethylene (PTFE) insert which was placed in an empty desorption tube prior to TD-GC analysis. The liquid standard mix consisted of ethanol (EtOH), acetone (Ace), dichloromethane (DCM) and chloroform (Chl) dissolved in toluene. Offline liquid calibration (OLC) was applied by introducing 2 μL of the standard mix under counter flow of an inert gas into the TD tube containing a mixed bed of mesoporous silica (MPSi) immobilized between two double layers of QF. The OLC results were verified using the inline liquid calibration (ILC) approach based on a heated GC injector installed on the TD. The validation results revealed that the proposed method has good recovery (> 98 %). R2-values (> 0.998) indicated good linearity over a wide range. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.01 and 0.04 μg on tube, respectively. Repeatability of the method was reported as RSD-values and they were lower than 3 %. A method based on the complete enzymatic digestion of albumin combined with conventional HS-GC was developed to verify the completeness of release of the RS from the albumin. Both the TD-GC and HS-GC methods were applied for the determination of EtOH and DCM in two different albumin samples loaded with experimental drugs. Statistical comparison indicated that there was no significant difference (p > 0.05) between the two methods. However, the HS-GC method following enzymatic degradation is much more expensive and time consuming.

Headspace GC/MS Analysis of Residual Solvents in Laminated Films Used for Food Packaging

Multilayer laminated films may contain organic solvents derived from adhesives, printing inks and so on. A headspace-GC/MS analysis method for the simultaneous determination of 30 substances such as toluene, xylene, acetone, methyl ethyl ketone, ethyl acetate, butyl acetate, methanol, ethanol, was developed. A N,N-dimethyl formamide solution containing an internal standard substance was added to the sample. After leaving overnight at room temperature, the headspace gas was analyzed by GC/MS. This method was applicable to a laminate film made of various materials. The organic solvents such as toluene, ethyl acetate, and heptane were detected from 6 out of 42 food packaging bags made from laminated film on Japanese market using this method.

Rhodamine B Purity Certified Reference Material

In this paper, we report the scientific details of the preparation and certification of pure Rhodamine B certified reference materials, including qualitative analysis, quantitative analysis, homogeneity test, stability test and uncertainty evaluation. Raw material of Rhodamine B was recrystallized for preparation of candidate reference material. The purified was dried, then bottled in dark glass vials. Infrared spectroscopy and nuclear magnetic resonance were used to determine the chemical composition of Rhodamine B. Homogeneity and stability assessments were performed, and the material was homogeneous enough. The results obtained from the stability assessment indicated that the Rhodamine B was stable. A cooperative certification was conducted with eight qualified laboratories by mass balance method (including analysis of liquid chromatography with diode array detector, water content, ash content and residual solvents analysis). The certified value of the reference material for purity was found to be 99.0% with a relative expanded uncertainty of 1.0% (k=2), which made the candidate reference material a very useful calibrant in food and cosmetic analysis.

SPME fiber coated by arrayed ZNRs for sampling and concentration of polar residual solvents for further analysis using GC FID

In this work, fused silica coated by arrayed ZNRs were successfully applied as a sorbent for analysis of polar residual solvents in pantoprazole feedstocks. ZnO nanoparticles were produced and deposited on a fused silica surface applying the dip coating technique and hydrothermal growth to synthesize the arrayed nanorods. The ZNRs array fiber coating was characterized by SEM, EDS, XRD, and TGA. The manufactured SPME fiber was coupled to a glass syringe of 10 μL and applied for the sampling of acetone, n-butanol, dichloromethane, ethyl acetate and methanol for further analysis using GC FID. Optimum operating conditions were determined for the incubation temperature (70 °C), incubation time (15 min), extraction time (120 s), and desorption time (0.6 min). Employing the optimum conditions, the proposed method resulted in a good linearity (> 0.997) and precision (< 7.1%) for the evaluated analytes. Recovery tests were also performed on three levels (below, equal to and above the ICH specification limit for residual solvents in pharmaceutical products). Recoveries ranging from 96% to 107% were obtained. Comparison between the reference method and developed method shows errors smaller than 4%.

Analysis of thermolabile residual solvents in a spray dried dispersion using static headspace gas chromatography.

In this study, we discuss the development of a static headspace gas chromatography method for the analysis of residual acetone as well as its enriched impurities including mesityl oxide and diacetone alcohol, in a spray dried dispersion. The major challenges include the instability of mesityl oxide and diacetone alcohol at high temperature and peak tailing of diacetone alcohol. It was found that the headspace oven temperature has to be controlled to 150°C or below to prevent degradation beyond an acceptable level (<1%). The peak tailing of diacetone alcohol was attributed to the "Phase Soaking" effect due to excessive diluent, which may condense and temporarily modify the stationary phase. The peak shape of diacetone alcohol is dependent on the column loading capacity and the peak area of N-methyl pyrrolidone, the solvent that elutes after diacetone alcohol. The headspace oven temperature was set at 140°C, where the highest response ratio of diacetone alcohol/N-methyl pyrrolidone at 1.46 and thus the best sensitivity was obtained. The calculated quantitation limits were 1ppm for acetone, 3ppm for mesityl oxide and 31ppm for diacetone alcohol. The method successfully passed validation criteria for specificity, linearity, accuracy, and precision.

A new matrix-matched calibration strategy for static headspace gas chromatography to enable high throughputs in pharmaceutical quality control laboratories

The analysis of residual solvents or generally, volatile organic substances using static headspace gas chromatography, is often accompanied by matrix effects.

Generic gas chromatography flame ionization detection method using hydrogen as the carrier gas for the analysis of solvents in pharmaceuticals

Within the pharmaceutical industry, the determination of residual solvents by Gas Chromatography Flame Ionization Detection (GC-FID) is a highly utilized analytical test that often employs helium (He) as the carrier gas. However, many do not realize that helium is a non-renewable resource that will eventually become progressively more difficult to source. In recent years, analytical chemists are increasingly adopting hydrogen (H2) in place of helium for routine GC analysis. In this study, a simple and efficient generic/universal GC-FID method using H2 as the carrier gas has been developed with the capability of baseline resolution of over 30 of the most commonly used solvents in development and manufacturing with a method run time of less than eight minutes. The use of this method for the separation and analysis of solvents within a pharmaceutical manufacturing process is demonstrated with additional method validation data presented using five different diluents as a means to increase flexibility for the chromatographer. Furthermore, it is the recommendation of the authors that the current compendia for residual solvent analysis be updated to allow for hydrogen as a carrier gas. The similarity between He and H2 observed within this study supports the use of hydrogen as a suitable replacement for helium, and an update of the EU and USP compendia for residual solvent analysis should be made to reflect this.

Determination and Quantitation of Residual Solvents in Natural Food Ingredients Using a Static Headspace Gas Chromatography with Flame Ionization Detection and Mass Spectrometric Detection Method

The determination of residual solvents is critical for quality control in food production and manufacturing processes. A gas chromatographic and mass spectrometric detection (MSD) method was developed and validated to complement the static headspace flame ionization detection (FID) technique for identification, confirmation, and quantitation of solvent residues in botanicals, using Coffeeberry extract and pomegranate powder as test samples. Relative standard deviations (RSDs) of less than 12% were obtained for residual solvents in water and dimethyl sulfoxide. Coffeeberry extract supplemented with10 μg/g of Residual Solvents Class 3 Mix showed MSD and FID recoveries mainly of 91 to 121% and 77 to 110%, respectively, while those samples supplemented with 100 μg/g of Residual Solvents Class 3 Mix displayed MSD and FID recoveries of 105 to 123% and 87 to 112%, respectively. For pomegranate samples supplemented with 10 μg/g of Residual Solvents Class 3 Mix, MSD and FID recoveries of 95 to 124% and 72 to 151% were observed, respectively. Those samples supplemented with 100 μg/g of Residual Solvents Class 3 Mix exhibited MSD and FID recoveries of 109 to 135% and 97 to 127%, respectively. Thus, the developed procedure was demonstrated to be suitable for the analysis of residual solvents in natural food ingredients and is expected to find numerous industrial applications (e.g., process control and impurity detection in final products).

Successful Development by Design of Experiments of a Gas Chromatography Method for Simultaneous Analysis of Residual Solvents of Classes 1 and 2.

In this study, design of experiments (DoE) was employed to develop a single injection method using a headspace gas chromatograph with flame ionization detector for resolution of residual solvents of United States Pharmacopeia (USP) listed classes 1 and 2, against current recommendation of independent injections. G43 column (6% cyanopropylphenyl and 94% dimethylpolysiloxane) and nitrogen were used as the stationary phase and carrier gas, respectively. Initial temperature, hold time, temperature ramp and carrier gas velocity were the critical method parameters. Resolution of 1,1,1-trichloroethane and tetrahydrofuan (THF); THF and chloroform; benzene and 1,2-dichloroethane (DCE), and 1,2-dimethoxyethane and DCE were selected as critical quality attributes. These were optimized by DoE that resulted in resolution of >1.34 among various solvents. The separation of all the solvents was achieved within total run time of 77 min. A better resolution of 2.66 was observed in the case of acetonitrile and methylene chloride; there was improved Signal/Noise ratio of 8.86 for 1,1,1-trichloroethane; tailing factor for pyridine was 1.00, and the method showed acceptable repeatability of peak areas (%RSDmax = 11.53) and retention times (%RSDmax = 0.45). Thus, while system suitability criteria and validation results very well met the USP requirements, the optimized method proposed in this study proved advantageous additionally in terms of single injection; short run time, and use of nitrogen as a carrier gas instead of costly helium in the USP method.

A Validated RP-HPLC Method for the Simultaneous Determination of Six High-Boiling Residual Solvents in Drug Substances and Its Implementation in Apis

A new method using high-performance liquid chromatography coupled with ultra violet detection was developed and validated for the simultaneous quantification of six high-boiling residual solvents-Acetic acid, N,N-dimethylformamide, Dimethyl sulfoxide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone and Benzyl alcohol in drug substances. This paper describes the development and validation of a simple and efficient RP-HPLC method for the determination of these high boiling residual solvents. Quantitation limits for Acetic Acid is 1000ppm (1000 μg/g of API), for Dimethylsulfoxide is 400 ppm (400 μg/g of API), for N, N dimethylformamide is 70 ppm (70 μg/g of API), for Dimethylacetamide is 80 ppm (80 μg/g of API), for N-methyl-2-pyrrolidone is 40 ppm (40 μg/g of API) and for Benzyl Alcohol is 60 ppm (60 μg/g of API) by this method. Several Active Pharmaceutical Ingredients were analyzed using the conditions of this method to evaluate and assess its versatility for the purpose of residual solvents analysis for a wide range of Active Pharmaceutical Ingredients. The results of this evaluation strongly indicate that this method can be readily used (as-is or with minor modifications) to determine high boiling residual solvents present in a wide range of Active Pharmaceutical Ingredients and other drug substances.

New nanoparticles obtained by co-assembly of amphiphilic cyclodextrins and nonlamellar single-chain lipids: Preparation and characterization

This work aimed at preparing new nanoscale assemblies based on an amphiphilic bio-esterified β-cyclodextrin (β-CD), substituted at the secondary face with n-decanoic fatty acid chains (β-CD-C10), and monoolein (MO) as new carriers for parenteral drug delivery. Stable binary (β-CD-C10/MO) and ternary (β-CD-C10/MO/stabilizer) nanoscale assemblies close to 100nm in size were successfully prepared in water by the solvent displacement method. The generated nanoparticles were fully characterized by dynamic light scattering, transmission electron microscopy, small-angle X-ray scattering, residual solvent analysis, complement activation and the contribution of each formulation parameter was determined by principal component analysis. The β-CD-C10 units were shown to self-organize into nanoparticles with a hexagonal supramolecular packing that was significantly modulated by the molar ratio of the constituents and the presence of a steric or electrostatic stabilizer (DOPE-PEG2000 or DOPA/POPA, respectively). Indeed, nanoparticles differing in morphology and in hexagonal lattice parameters were obtained while the co-existence of multiple mesophases was observed in some formulations, in particular for the β-CD-C10/MO/DOPA and β-CD-C10/MO/POPA systems. The mixed β-CD-C10/MO/DOPE-PEG2000 nanoparticles (49:49:2 in mol%) appeared to be the most suitable for use as a drug delivery system since they contained a very low amount of residual solvent and showed a low level of complement C3 activation.

Use of ionic liquids as headspace gas chromatography diluents for the analysis of residual solvents in pharmaceuticals

In this study, two ionic liquids (ILs), 1-butyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([BMIM][NTf2]) and trihexyltetradecylphosphonium bis[(trifluoromethyl)sulfonyl]imide ([P66614][NTf2]) were examined as contemporary diluents for residual solvent analysis using static headspace gas chromatography (SHS-GC) coupled with flame ionization detection (FID). ILs are a class of non-molecular solvents featuring negligible vapor pressure and high thermal stabilities. Owing to these favorable properties, ILs have potential to enable superior sensitivity and reduced interference, compared to conventional organic diluents, at high headspace incubation temperatures. By employing the [BMIM][NTf2] IL as a diluent, a 25-fold improvement in limit of detection (LOD) was observed with respect to traditional HS-GC diluents, such as N-methylpyrrolidone (NMP). The established IL-based method demonstrated LODs ranging from 5.8 parts-per-million (ppm) to 20ppm of residual solvents in drug substances. The optimization of headspace extraction conditions was performed prior to method validation. An incubation temperature of 140°C and a 15min incubation time provided the best sensitivity for the analysis. Under optimized experimental conditions, the mass of residual solvents partitioned in the headspace was higher when using [BMIM][NTf2] than NMP as a diluent. The analytical performance was demonstrated by determining the repeatability, accuracy, and linearity of the method. Linear ranges of up to two orders of magnitude were obtained for class 3 solvents. Excellent analyte recoveries were obtained in the presence of three different active pharmaceutical ingredients. Owing to its robustness, high throughput, and superior sensitivity, the HS-GC IL-based method can be used as an alternative to existing residual solvent methods.

Chromatoprobe as a sample-sparing technique for residual solvent analysis of drug discovery candidates by gas chromatography

In drug discovery research, residual solvent measurement is an integral part of purity analysis for synthesis of a drug candidate before it is used for toxicity testing. This is usually carried out using gas chromatography (GC) with direct injection sample introduction. This method requires testing compounds to be soluble at high concentrations (>50mg/mL, usually in DMSO) to achieve acceptable sensitivity, a hurdle which is not always achievable for some samples such as cyclic peptides and oligonucleotides. To overcome the limitation associated with the direct injection approach, a new method using the Chromatoprobe thermal extraction device was developed for quantifying residual solvents of drug discovery compounds. This method not only consumes significantly less material (less than 1mg), but also shows higher sensitivity than the direct injection approach. In addition, because no diluent is required with the Chromatoprobe thermal extraction, all residual solvents can be detected and measured without further method optimization. In our study, we compared data from GC residual solvent analysis using the Chromatoprobe solid sample introduction to those of the direct injection method for seven in-house samples. Our results showed a good agreement between the data from these two sample introduction methods. Thus, the Chromatoprobe sample introduction method provided a sample-sparing alternative to the direct injection method for the measurement of residual solvents in drug discovery. This method can be particularly useful for residual solvent analysis in samples that are available only in limited amounts, poorly soluble, and/or unstable in the diluents used for the direct injection method.

Analysis of residual solvent in thickeners by headspace gas chromatography using a standard addition method

Headspace gas chromatography (HS-GC) is an accepted method for analysis of residual solvents in pharmaceuticals, food additives and food. The amounts of residual solvent present in various food thickeners were analysed by HS-GC standard addition method. Conditions for the HS-GC were optimised, and equilibration time was determined to be 40 min at 60°C for the determination of residual solvent. The results were very similar to those obtained by distillation and gas chromatography (Distillation-GC). We conclude that both methods are equally efficient for the determination of residual solvent in thickeners. In addition capillary column (Aquatic-2 GL Sciences Co.) was used to analyze by headspace or distillation. Corresponding author: Chiye Tatebe, Division of Food Additives, National Institute of Health Sciences, 1-18-1, Kami-yoga, Tokyo 158-8501, Japan

Development of transmucosal patch loaded with anesthetic and analgesic for dental procedures and in vivo evaluation.

Most of the dental surgeries require preoperative anesthetic and postoperative analgesic for painless procedures. A multidrug transmucosal drug delivery system loaded with lignocaine (Lig) base for immediate release and solid lipid nanoparticles (SLNs) of diclofenac (Dic) diethylamine for prolonged release was developed. SLNs were prepared by solvent emulsion–evaporation method with Precirol ATO 5 and Geleol as lipids and Pluronic F 68 as surfactant and optimized with Box–Behnken design for particle size and entrapment efficiency. SLNs were incorporated into the transmucosal patch (TP) prepared with hydroxypropyl cellulose-LF (HPC-LF) and with a backing layer of ethyl cellulose. Optimized SLNs and TP were characterized for Fourier transform infrared spectrophotometry, differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, in vitro release, ex vivo permeation through porcine buccal mucosa, Caco-2 permeability, and residual solvent analysis by gas chromatography. The TP was also evaluated for swelling index, in vitro residence time, tensile strength, and mucoadhesive strength. Preclinical pharmacokinetic, pharmacodynamic, and histopathological studies by application of TP on the gingiva of New Zealand rabbits were carried out. Particle size and entrapment efficiency of the optimized SLN “S8” were determined as 98.23 nm and 84.36%, respectively. The gingival crevicular fluid and tissue concentrations were greater than plasma concentrations with increase in Cmax and area under the curve (AUC) of Lig and Dic when compared to the control group. Pain perception by needle prick showed prolonged combined anesthetic and analgesic effect. The developed TP loaded with Lig base and Dic diethylamine-SLNs exhibited immediate and complete permeation with tissue accumulation of Lig followed by controlled prolonged release and tissue accumulation of Dic at the site of application. Thus, it could be anticipated from the in vivo studies that the developed TP provides immediate initial anesthetic effect, and the analgesic effect would be prolonged for 24 hours, since optimal gingival crevicular fluid and tissue levels of analgesic would be achieved, while the tissue remains anesthetized.

Development of an Automated Headspace Gas Chromatography Instrument for the Determination of Residual Solvents in Pharmaceutical Compounds and Reaction Mixtures

The use of gas chromatography with headspace sampling is commonplace in analytical laboratories for the analysis of residual solvents. In this article, we discuss the use of an internal standard-based calibration, utilizing relative response factors, to enable the generation of accurate weight % solvent data on 25 common solvents in a single chromatographic run. The total cycle time for analysis is less than 30 min. To facilitate this technology into the process chemistry environment, bespoke open access software has been developed to simplify the sample submission process such that virtually no training is required to analyze the sample, process the data, and generate a report. Furthermore, an automated calibration check workflow has been implemented to validate the quality of the data on a daily basis and alert the system administrator in the event of a problem with the system.