Optimization of microwave-assisted extraction for alizarin and purpurin in Rubiaceae plants and its comparison with conventional extraction methods

A simple and rapid microwave-assisted extraction (MAE) procedure was developed and optimized for two common color pigments, alizarin and purpurin, in various samples of Rubiaceae plants. Several variables that can potentially affect the extraction efficiency, namely temperature, methanol concentration in the extractant mixture, time, and solvent volume were optimized by means of a central composite design approach. The results suggest that temperature and methanol concentration in the solvent mixture are statistically the most significant factors. The separation and quantitative determination of the pigments was carried out in less than 6 min by a developed high-performance liquid chromatographic method with UV detection at 250 nm. Under optimum operating conditions, MAE showed significantly higher recoveries than those obtained by the conventional extraction methods (ultrasonic and reflux extraction), ranging from 84 to 94%. In addition, a drastic reduction of the extraction time (20 min versus 6 h) and solvent consumption (20 versus 100 mL) was achieved with a reproducibility (RSDs < 10%) comparable with that provided by the reflux extraction as a reference method.     

Microwave-assisted extraction of phenolics from Canarium album L. and identification of the main phenolic compound

Microwave-assisted extraction (MAE) was applied in the extraction of phenolics from Canarium album L. Effects of various conditions including the solvent, solvent to material ratio, microwave power and irradiation time on extraction yield of phenolics were investigated. In terms of the optimal conditions of MAE, it was concluded that 70% (v/v) of ethanol was the proper extraction solvent, the solvent to material ratio was 10 : 1 (mL : g), and the microwave power and irradiation time were 600 W and 15 s, respectively. Compared with normal stirring extraction and ultrasound-assisted extraction, the MAE of phenolics from C. album L. was more time efficient and gave a high extraction rate. More than 1.2% extraction yield was achieved with MAE, and the purity of the phenolics in the extract product was up to 25%. In addition, by ultraviolet-visible (UV) spectrometry and electrospray ionised mass spectrometry (ESI/MS), the main phenolic compound in the extract product was identified as gallic acid.     

Optimisation of a microwave-assisted extraction method for the simultaneous determination of haloanisoles and halophenols in cork stoppers

This study presents a method based on the use of microwave-assisted extraction (MAE) for the quantitative analysis of 2,4,6-trichloroanisole (TCA), 2,3,4,6-tetrachloroanisole (TeCA), pentachloroanisole (PCA), 2,4,6-tribromoanisole (TBA), 2,4,6-trichlorophenol (TCP), 2,3,4,6-tetrachlorophenol (TeCP), pentachlorophenol (PCP) and 2,4,6-tribromophenol (TBP) in cork stoppers. The influential parameters of the MAE procedure (extraction time, temperature and solvent volume) were optimised using a central composite experimental design combined with desirability functions. The optimal conditions identified were temperature 170 degrees C, solvent volume 35 mL and extraction time 90 min. MAE extracts were concentrated and derivatised prior to separation and quantification by gas chromatography with electron capture detection. To evaluate the applicability of the proposed MAE method, recovery results were compared with those obtained with the Soxhlet extraction method; the results were similar with both extraction methods. The new method was also satisfactorily applied to real cork stopper samples.     

Microwave‐assisted extraction followed by RP‐HPLC for the simultaneous extraction and determination of forsythiaside A,rutin, and phillyrin in the fruits of Forsythia suspensa

An optimized microwave‐assisted extraction (MAE) method and RP‐HPLC method were developed for the simultaneous extraction and determination of rutin, forsythiaside A, and phillyrin in the fruits of Forsythia suspensa. The key parameters of the open‐vessel MAE process were optimized. A mixed solvent of methanol and water (70:30, v/v) was most suitable for the simultaneous extraction of the three components. The sample was soaked for 10 min before extraction. The optimized conditions were: microwave power 400 W, temperature 70°C, solvent‐to‐material ratio 30 mL/g, and extraction time 1 min. Compared to conventional extraction methods, the proposed method can simultaneously extract the three components in high yields and was proved to be a more rapid method with a lower solvent consumption. The optimized HPLC–photodiode array detection analysis was validated to have good linearity, precision, accuracy, and sensitivity. The developed MAE followed by RP‐HPLC is a fast and appropriate method for the simultaneous extraction and determination of rutin, forsythiaside A, and phillyrin in the fruits of F. suspensa.     

Microwave-assisted extraction of active pharmaceutical ingredient from solid dosage forms

The microwave assisted extraction (MAE) technique has been evaluated for the extraction of active pharmaceutical ingredients (API) from various solid dosage forms. Using immediate release tablets of Compound A as a model, optimization of the extraction method with regards to extraction solvent composition, extraction time and temperature was briefly discussed. Complete recovery of Compound A was achieved when samples were extracted using acetonitrile as the extraction solvent under microwave heating at a constant cell temperature of 50 degrees C for 5 min. The optimized MAE method was applied for content uniformity (single tablet extraction) and potency (multiple tablets extraction) assays of release and stability samples of two products of Compound A (5 and 25mg dose strength) stored at various conditions. To further demonstrate the applicability of MAE, the instrumental extraction conditions (50 degrees C for 5 min) were adopted for the extraction of montelukast sodium (Singulair) from various solid dosage forms using methanol-water (75:25, v/v) as the extraction solvent. The MAE procedure demonstrated an extraction efficiency of 97.4-101.9% label claim with the greatest RSD at 1.4%. The results compare favorably with 97.6-102.3% label claim with the greatest RSD at 2.9% obtained with validated mechanical extraction procedures. The system is affordable, user-friendly and simple to operate and troubleshoot. Rapid extraction process (7 min/run) along with high throughput capacity (up to 23 samples simultaneously) would lead to reduced cycle time and thus increased productivity.     

Separation and purification of furanocoumarins from Toddalia asiatica (L.) Lam. using microwave-assisted extraction coupled with high-speed counter-current chromatography

A method of microwave-assisted extraction coupled with high-speed counter-current chromatography was established for separation and purification of isopimpinellin, pimpinellin and phellopterin from Toddalia asiatica (L.) Lam. The conditions of MAE including the extraction solvent, size of sample, solid/liquid ratio, extraction temperature and extraction time were optimized by a mono-factor test. That is, 2.0 g dried powder of T. asiatica (L.) Lam of 0.30-0.15 mm size was extracted with 20 mL (solid/liquid ratio of 1:10, g/mL) methanol under 50 °C for 1 min. The crude extract was separated and purified by high-speed counter-current chromatography with hexane-ethyl acetate-methanol-water (5:5:5.5:4.5, v/v/v/v) solvent system. 0.85 mg/g of isopimpinellin, 2.55 mg/g of pimpinellin and 0.95 mg/g of phellopterin were obtained from original sample in one-step within 240 min, the purity determined by high performance liquid chromatography was 95.0%, 99.1% and 96.4%, respectively. Their chemical structures were further identified by mass spectroscopy and nuclear magnetic resonance spectroscopy. The results demonstrated that microwave-assisted extraction coupled with high-speed counter-current chromatography was a feasible, economical and efficient technique for rapid extraction, separation and purification of effective compounds from natural products.     

Optimization of Microwave-Assisted Extraction for the Determination of Glycyrrhizin in Menthazin Herbal Drug by Experimental Design Methodology

In the present study, a microwave-assisted extraction (MAE) method has been investigated for the extraction of glycyrrhizin from Menthazin herbal drug. The extracted samples have been analyzed by a developed reversed-phase liquid chromatography with ultraviolet detection. The separation was performed by a Eurospher-100 C₈ reversed-phase column (250 × 4.6 mm i.d., 5 μm) and the mobile phase consisted of methanol:acetonitrile:water:glacial acetic acid (30:30:40:1 v/v/v/v) with a flow rate of 0.8 mL min^?1. The extraction procedure has been screened by a two level full factorial design for determination of statistically significant parameters. Thereafter, the identified parameters, extraction temperature, time and solvent volume were optimized by a Box–Behnken design. The proposed mathematical model was based on analysis of variance results and correctly explained the behavior of the response in the experimental domain. R ² value adjusted for numbers of degrees of freedom was 0.9915 and P-value for lack of fit, 0.8499 at the 95% confidence level, P > 0.05. The optimal condition identified were extraction temperature, 70 °C, time, 13.8 min and solvent volume 2.0 mL. To evaluate the applicability of the proposed MAE method, results were compared with those obtained with the liquid extraction method. Extraction efficiency and precision were higher when MAE has been used. The proposed method allows extracting the glycyrrhizin in a small quantity of solvent and faster than the liquid extraction method.     

小白菜中残留虫酰肼的超临界流体萃取条件的研究

将超临界流体萃取(supercritical fluid extraction,SFE)技术与高效液相色谱分析相结合,建立了特异性杀虫剂虫酰肼的萃取分离方法。SFE对虫酰肼的萃取条件:压力48.3 MPa(7000 psi),温度60 ℃,静态萃取时间20 min,CO2体积10 mL,改性剂甲醇添加量0.04 mL/g,丙酮为收集溶剂。在此条件下,SFE对虫酰肼的萃取率为100.75%,所得样品可直接用于高效液相色谱分析。色谱条件：紫外-二极管阵列检测器(检测波长为245 nm),C18键合色谱柱,乙腈     

Rapid method for the determination of organochlorine pesticides and PCBs in fish muscle samples by microwave-assisted extraction and analysis of extracts by GC-ECD

A procedure for the multiresidue determination of organochlorine pesticides and polychlorinated biphenyls in fish muscle samples has been developed. The method is based on the microwave-assisted extraction (MAE) of food samples from an acetonitrile-water (95 + 5, v/v) mixture followed by SPE cleanup of the extracts and analysis by GC with an electron capture detector. MAE operational parameters, such as the extraction solvent, temperature, and time, were optimized with respect to the extraction efficiency of the target compounds from food samples with 10-13% fat content. The chosen extraction technique allows reduction of the solvent consumption and extraction time when compared with methods already used. Acetonitrile is a good extraction solvent for low-fat matrixes (2-20% fat content), such as fish samples, because it does not significantly dissolve the highly polar proteins, salts, and sugars commonly found in food and gives high recoveries of a wide polarity range of analytes. For purification, SPE using LC-Florisil was shown to be sufficient for the removal of coextracted substances. Recoveries > 78% with RSD values < 15% were obtained for all compounds under the selected conditions. Method quantification limits were in the 5-10 microg/kg range. The method was applied to the analysis of samples of herring (Clupea harengus) purchased at the local fish market. The method is rapid and reliable for the determination of organochlorine analytes in fish muscle.     

Determination of main taxoids in Taxus species by microwave‐assisted extraction combined with LC‐MS/MS analysis

A method based on microwave‐assisted extraction (MAE) has been developed for the determination of paclitaxel and five related taxoids, namely 10‐deacetylbaccatin III (10‐DAB III), cephalomannine, 10‐deacetylpaclitaxel (10‐DAT), 7‐xyl‐10‐ deacetylpaclitaxel (7‐xyl‐10‐DAT), and 7‐epi‐10‐deacetylpaclitaxel (7‐epi‐10‐DAT) in Taxus species in this study. The influential parameters of the MAE procedure were optimized, and the optimal conditions were as follows: extraction solvent 80% ethanol solution, solid/liquid ratio 1:10 (g/mL), temperature 50°C, and three extraction cycles, each cycle 10 min. The method validation for LC‐MS/MS analysis was performed. The LOD and LOQ were 3.16–9.20 and 12.20–30.45 ng/mL, respectively. Repeatability and reproducibility for the six taxiods with RSD ranged from 2.78 to 3.85% and from 5.26 to 6.60%. The recoveries of the method for the six taxoids were 92.6–105.6%. The developed MAE‐LC‐MS/MS method was also successfully applied to determine the contents of six taxoids in different Taxus species.     

Application of accelerated solvent extraction to the investigation of saikosaponins from the roots of Bupleurum falcatum

Accelerated solvent extraction (ASE) was applied to the extraction of saikosaponin a, saikosaponin c and saikosaponin d from the roots of Bupleurum falcatum. Main extraction parameters such as the extraction solvents, extraction temperature and static extraction time were investigated and optimized. The optimized procedure employed 70% methanol as extraction solvent, 120°C of extraction temperature, 10 min of static extraction time, 60% of flush volume and the extraction recoveries of the three compounds were near to 100% with one extraction cycle. The extracted samples were analyzed by HPLC with UV detector. The HPLC conditions were as follows: Hypersil ODS2 (4.6 mm×250 mm, 5 μm) column, acetonitrile and water as mobile phase, flow rate of 1.0 mL/min, UV detection wavelength of 204 nm and injection volume of 20 μL. Compared with the traditional methods including heat‐reflux extraction and ultrasonic‐assisted extraction, the proposed ASE method was more efficient and faster to be operated. The results indicated that ASE was an alternative method for extracting saikosaponins from the roots of B. falcatum.     

A cost effective,sensitive, and environmentally friendly sample preparation method for determination of polycyclic aromatic hydrocarbons in solid samples

A simple, cost effective, and yet sensitive sample preparation technique was investigated for determining Polycyclic Aromatic Hydrocarbons (PAHs) in solid samples. The method comprises ultrasonic extraction, Stir Bar Sorptive Extraction (SBSE), and thermal desorption–gas chromatography–mass spectrometry to increase analytical capacity in laboratories. This method required no clean-up, satisfied PAHs recovery, and significantly advances cost performance over conventional extraction methods, such as Soxhlet and Microwave Assisted Extraction (MAE). This study evaluated three operational parameters for ultrasonic extraction: solvent composition, extraction time, and sample load. A standard material, SRM 1649 a (urban dust), was used as the solid sample matrix, and 12 priority PAHs on the US Environmental Protection Agency (US EPA) list were analyzed. Combination of non-polar and polar solvents ameliorated extraction efficiency. Acetone/hexane mixtures of 2:3 and 1:1 (v/v) gave the most satisfactory results: recoveries ranged from 63.3% to 122%. Single composition solvents (methanol, hexane, and dichloromethane) showed fewer recoveries. Comparing 20 min with 60 min sonication, longer sonication diminished extraction efficiencies in general. Furthermore, sample load became a critical factor in certain solvent systems, particularly MeOH. MAE was also compared to the ultrasonic extraction, and results determined that the 20-min ultrasonic extraction using acetone/hexane (2:3, v/v) was as potent as MAE. The SBSE method using 20 mL of 30% alcohol-fortified solution rendered a limit of detection ranging from 1.7 to 32 ng L⁻¹ and a limit of quantitation ranging from 5.8 to 110 ng L⁻¹ for the 16 US EPA PAHs.     

Microwave-assisted extraction of coumarin and related compounds from Melilotus officinalis (L.) Pallas as an alternative to Soxhlet and ultrasound-assisted extraction

Soxhlet extraction, ultrasound-assisted extraction (USAE) and microwaves-assisted extraction (MAE) in closed system have been investigated to determine the content of coumarin, o-coumaric and melilotic acids in flowering tops of Melilotus officinalis. The extracts were analyzed with an appropriate HPLC procedure. The reproducibility of extraction and of chromatographic analysis was proved. Taking into account the extraction yield, the cost and the time, we studied the effects of extraction variables on the yield of the above-mentioned compounds. Better results were obtained with MAE (50% v/v aqueous ethanol, two heating cycles of 5 min, 50 degrees C). On the basis of the ratio extraction yield/extraction time, we therefore propose MAE as the most efficient method.     

Desirability function approach for the optimization of an in‐syringe ultrasound‐assisted emulsification‐microextraction method for the simultaneous determination of amlodipine and nifedipine in plasma samples

In the present study, an in‐syringe ultrasound‐assisted emulsification‐microextraction using a low‐density organic solvent was developed for simultaneous extraction and pre‐concentration of amlodipine besylate and nifedipine from plasma samples. The extracts were analyzed by high‐performance liquid chromatography with UV detection. Central composite design combined with desirability function was applied to find out the optimal experimental conditions providing the highest global extraction efficiency. The optimal conditions identified were volume of the extracting solvent 45 μL, ionic strength 18.95% w/v, sonication time 2.58 min, and centrifugation time 3 min. Under the optimal conditions, the proposed method was evaluated, and applied to the analysis of amlodipine besylate and nifedipine in plasma samples. The validation results of the method indicated a wide linear range (2–1200 ng/mL) with a good linearity (r² >0.9991) and low detection limits (0.17 ng/mL for amlodipine besylate and 0.15 ng/mL for nifedipine) with RSD less than 5.2% for both components, both in intra‐ and inter‐day precision studies. The applicability of the proposed in‐syringe ultrasound‐assisted emulsification‐microextraction coupled to high‐performance liquid chromatography with UV detection method was demonstrated by analyzing the drugs in spiked plasma samples.     

Microwave-assisted extraction of OCPs, PCBs and PAHs concentrated by semi-permeable membrane devices (SPMDs)

Microwave-assisted extraction (MAE) has been evaluated as an alternative to dialysis for extraction of some water-borne hydrophobic contaminants sampled by semi-permeable membrane devices (SPMDs). Seven organochlorine pesticides (OCPs), 11 polychlorinated biphenyls (PCBs) and 13 polycyclic aromatic hydrocarbons (PAHs) were accumulated in SPMDs at nanogram levels and extracted with three 3-min irradiation cycles with 33 mL of a solvent mixture hexane–water (10:1,v/v) in each cycle. The developed MAE method gave for all analytes investigated statistically comparable extraction yields with those found by dialysis carried out with a total volume of 250 mL hexane for 48 h at room temperature. The recoveries of all the targeted contaminants were in the range of 65–105% with variation coefficients not exceeding 19%. The applicability of the MAE extraction was tested in field SPMDs samples deployed for 15 days in a sewage-treatment process. Our results show that MAE provides a remarkable reduction of time and solvent volume when used as an extraction method in the analysis of SPMDs.     

Determination of dieldrin in wool products by gas chromatography with microwave-assisted extraction

Dieldrin is a moth-proofing agent that was banned by the Stockholm Convention in 2001. The amount of dieldrin in wool products was measured by a microwave-assisted extraction (MAE) method. The optimal conditions were as follows: extraction solvent, acetone/n-hexane (1:1 v/v); extraction temperature, 110 degrees C; extraction time, 10 min; solvent volume, 25 mL. When six samples were used, dieldrin contents determined by GC with the proposed MAE agreed closely with those by the Japanese official method using GC with solvent extraction and cleanup by column chromatography. The proposed MAE has two merits. First, the pretreatment of the MAE needs only 4 h for 11 samples, while that using the Japanese official method needs 2 days for six samples. Second, the volume of organic solvents used for the proposed method was only about one-tenth of that used in the Japanese official method. Our proposed method seems to be easy and useful for daily (routine) tests. Dieldrin contents of 28 used wool products, which were obtained from local clothing shops and ordinary homes, were determined by GC with the proposed MAE, and six products contained dieldrin (0.310-175 ppm). The dry cleaning of the woolen yarn containing 175 ppm dieldrin did not remove a significant amount of dieldrin. Therefore, it seems likely that dieldrin is still distributed slightly but widely throughout the world.     

Experimental design for optimization of microwave-assisted extraction of benzodiazepines in human plasma

A simple and fast microwave-assisted-extraction (MAE) method has been evaluated as an alternative to solid-phase extraction (SPE) for the determination of six benzodiazepines widely prescribed in European countries (alprazolam, bromazepam, diazepam, lorazepam, lormetazepam and tetrazepam) in human plasma. For MAE optimization a Doehlert experimental design was used with extraction time, temperature and solvent volume as influential parameters. A desirability function was employed in addition to the simultaneous optimization of the MAE conditions. The analysis of variance showed that the solvent volume had a positive influence on the extraction of all the analytes tested, achieving a statistically significant effect. Also, the extraction time had a statistically significant effect on the extraction of four benzodiazepines. The selected MAE conditions—89 °C, 13 min and 8 mL of chloroform/2-propanol (4:1, v/v)—led to recoveries between 89.8 ± 0.3 and 102.1 ± 5.2% for benzodiazepines using a high performance liquid chromatography method coupled with diode-array detection. The comparison of MAE and SPE shows better results for MAE, with a lower number of steps in handling the sample and greater efficiency. The applicability of MAE was successfully tested in 27 plasma samples from benzodiazepine users.     

An improved method for simultaneous analysis of steroid and phenolic endocrine disrupting chemicals in biological samples

An improved method was developed for the simultaneous determination of eight steroid and phenolic endocrine disrupting chemicals, such as oestrone (E1), 17β-oestradiol (E2), oestriol (E3), 17α-ethynylestradoil (EE2), 4-nonylphenol (4-NP), bisphenol A (BPA), 4-tert-octylphenol (4-t-OP) and 4-cumylphenol (4-CP), in biological samples. The optimal extraction and clean-up procedures were investigated using microwave-assisted extraction (MAE), automated gel permeation chromatography (GPC) and solid phase extraction (SPE). As a consequence, the most efficient extraction was achieved by using MAE with methanol as solvent at an extraction temperature of 110°C for 20?min. The clean-up of extracts was carried out by GPC on a Biobeads S-X3 column with cyclohexane/ethyl acetate (1:1, v/v) as mobile phase. Target compounds were eluted in the fraction from 7–14?min retention time. Moreover, the cleanest extracts were obtained by solid phase extraction with C-18 cartridges after the elution with 15?mL ethyl acetate. The final sample extracts were derivatised using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) (1% trimethylchlorosilane, TMCS) as derivatisation reagent with pyridine as the solvent. Quantification was performed by gas chromatography-mass spectrometry (GC-MS) with electron ionisation (EI) and selected ion monitoring (SIM) mode. The method was validated by spiked samples which showed good recovery and reproducibility. The overall recoveries ranged between 55.1% and 100.6%, with relative standard deviations (RSD) of 2.3–12.7% for the entire procedure. Method detection limits (MDL) ranged from 0.3 to 0.7?ng?g^?1 dry weight (dw). Performance of the method was demonstrated by its application on tissues from fish exposed to high concentration of EDCs in the laboratory. The developed method is a promising approach for the analysis of steroid and phenolic endocrine disrupting chemicals in various biological samples.     

Comparison of techniques for the extraction of the anti-cancer drug camptothecin from Nothapodytes foetida

Extraction methods using stirring extraction, Soxhlet extraction, ultrasonic extraction and microwave-assisted extraction (MAE) were evaluated for the percentage extraction of camptothecin (CPT) and 9-methoxycamptothecin (9-Me-CPT) from Nothapodytes foetida. The extracts were analyzed by high performance liquid chromatography (HPLC). Methanol (90%, v/v) extracted high percentage extraction of CPT and 9-Me-CPT compared to ethanol (90%, v/v). The results shows that the percentage extraction of CPT and 9-Me-CPT from N. foetida by MAE was more efficient in short time followed by Soxhlet extraction, ultrasonic and stirring extraction methods. Maximum percentage extraction of CPT (2.67%, w/w) was obtained by MAE technique. MAE has need of 3 min, whereas ultrasonic extraction, Soxhlet extraction and stirring extraction techniques require 30, 120 and 30 min, respectively to leach higher percentage extraction of CPT and 9-Me-CPT. The times taken by the microwave extraction process was 40 times less than the Soxhlet extraction for percentage extraction of alkaloids. The present results show that the extraction efficiency and considerable saving of time by MAE was more competent than the other extraction techniques.     

An efficient diethyl ether-based soxhlet protocol to quantify faecal sterols from catchment waters

A study was conducted to evaluate the efficiency and reproducibility of a diethyl ether-based soxhlet extraction procedure for faecal sterols occurring from catchment waters. Water samples spiked with a mixture of faecal sterols were filtered and analytes were extracted using the diethyl ether-based soxhlet method and the Bligh and Dyer chloroform extraction process. For diethyl ether-based soxhlet extraction procedure, solvent extracts were saponified with 100 microL of 10% KOH in methanol (100 degrees C/120 min) and then acidified with 60 microL of 6M HCl. Lipid contents were extracted by ethanol (0.5 mL) from the saponification products. The lipid extracts were then reacted with 100 microL of bis(trimethyl)trifluoroacetamide (BSTFA) containing 1% trimethyl chlorosilane (100 degrees C/60 min) to form the trimethylsilyl (TMS) derivatives. The derivatised extracts were then analyzed by gas chromatography-mass spectrometry. For sterol concentrations ranging from 35 to 175 microg mL(-1), the soxhlet-based extraction process yielded the following recovery efficiencies for coprostanol (101%), epicoprostanol (97%), cholesterol (97%), dihydrocholesterol (97%) and 5alpha-cholestane (111%), whereas the Bligh and Dyer process yielded recoveries of 32, 41, 0, 36 and 51%, respectively. The results suggested that the diethyl ether-based soxhlet extraction method was more efficient and reproducible than the Bligh and Dyer chloroform extraction process for the analyses of trace levels of faecal sterols from water samples. Moreover, it was revealed that the diethyl ether-based soxhlet extraction method used less solvent and was logistically easier.