Methacrylic Acid-ethylene Glycol Dimethacrylate Research Articles

Determination of ligustrazine in rat serum by polymer monolithic micro-extraction combined with ultra high performance liquid chromatography-tandem mass spectrometry

AbstractThis study focused on developing an effective and environmentally friendly method to measure ligustrazine in rat serum by using polymer monolith micro-extraction (PMME) technique. A poly (methacrylic acid-ethylene glycol dimethacrylate) material was used to extract ligustrazine through hydrophobic and ion-exchange interaction. Qualitative and quantitative analysis was performed by a liquid chromatography and tandem mass spectrometry. After optimization of several PMME conditions, the developed method exhibited excellent extraction performance to the ligustrazine. Good linearity was acquired ranging from 10 to 2,000 ng mL−1, and the limit of detection of the proposed method was 0.14 ng mL−1. The recoveries measured by spiking three different concentrations in rat serum ranged from 82.6 to 95.3%, and excellent precision was found with relative standard deviations (RSDs) less than 8.3% for intra-day and 9.7% for inter-day, respectively. At last, the applicability of the method was further confirmed through continuous monitoring of ligustrazine in rat serum after dosing of ligustrazine tablets to rats.

Recyclable Cu(II)-(MAA-EGDMA) catalyst for selective oxidation of alcohols to aldehydes using sodium hypochlorite

Copper(II) α-benzoin oxime complex was synthesized by the reaction between copper(II) benzoate and α-benzoin oxime. The poly methacrylic acid-ethylene glycol dimethacrylate (MAA-EGDMA) was applied as support of copper complex catalyst for oxidation of alcohols to aldehydes using NaClO. The structure and morphology of immobilized Cu(II)-benzoin oxime have been studied by using different analysis including Fourier Transform Infrared (FT-IR) spectroscopy, Scanning Electron Microscopy (SEM) and Thermal Gravimetric Analysis (TGA). The yield of aldehydes was determined by Gas Chromatography (GC) analysis. The immobilized Cu(II)-benzoin oxime indicated a high catalytic activity compared to its absence for the alcohol oxidation with sodium hypochlorite. The effect of the reaction time and temperature, the solvent type, the amounts of catalyst and NaClO were optimized to obtain maximum yield. The prepared catalyst had various benefits such as being inexpensive, environmentally friendly manner, recyclable, reducing the reaction time and increasing the yield. A reaction mechanism is proposed for oxidation of alcohols in the presence of the catalyst.

Methacrylic acid-ethylene glycol dimethacrylate polymeric sorbent for the removal of estrogens from water

Methacrylic acid-ethylene glycol dimethacrylate polymeric sorbent for the removal of estrogens from water

Molecularly imprinted based solid phase microextraction method for monitoring valproic acid in human serum and pharmaceutical formulations

In this paper, a straightforward method is presented to detect valproic acid after its microextraction. Molecularly imprinted polymer fiber was used in conjunction with chromatography-flame ionization to achieve this goal. A narrow bore silica capillary was adopted as a mold, via the copolymerization of meth acrylic acid–ethylene glycol dimethacrylate imprinted with VPA, to synthesize the fiber. Extraction temperature, extraction time, salt addition, pH, stirring rate, and desorption temperature—all of which are factors that can influence the extraction process—were measured, and adjusted accordingly. Linearity, precision, and detection limits, as analytical elements, were also evaluated under optimum conditions. Readings showed a linear range of 0.03–100 µg L− 1 (r2 = 0.998), and the limit of detection was measured as 0.01 µg L− 1. The established method was then applied in selective detection of valproic acid in tablet, syrup and human serum samples successfully.

Poly(methacrylic acid-ethylene glycol dimethacrylate-N-vinylcarbazole) monolithic column for the enrichment of trace benzodiazepines from urine and beer samples.

A sensitive microextraction method based on a new poly(methacrylic acid-ethylene glycol dimethacrylate-N-vinylcarbazole) monolithic capillary column, coupled with gas chromatography and electron capture detection, was established for the determination of three benzodiazepines (estazolam, alprazolam, and triazolam) in urine and beer samples. Owing to the abundant π electrons and polar surface of N-vinylcarbazole, N-vinylcarbazole-incorporated monolith showed a higher extraction performance than neat poly(methacrylic acid-ethylene glycol dimethacrylate) because of the enhanced π-π stacking interactions derived from the π-electron-rich benzene groups from N-vinylcarbazole. The monolith exhibited a homogeneous and continuous structure, good permeability, and a long lifetime. Factors affecting the extraction such as solution pH, salt concentration, sample volume, desorption solvent, and desorption volume were investigated. Under the optimized conditions, limits of detection of 0.011-0.026ng/mL were obtained. The one-column and column-to-column precision values were ≤7.2 and ≤9.8%, respectively. The real samples were first diluted with deionized water and then treated by the monolith microextraction before gas chromatography analysis. The recoveries were 81.4-93.3 and 83.3-94.7% for the spiked samples, with relative standard deviations of 4.1-8.1 and 3.8-8.5%, respectively. This method provides an accurate, simple, and sensitive detection platform for drug analysis.

Selective determination of thidiazuron herbicide in fruit and vegetable samples using molecularly imprinted polymer fiber solid phase microextraction with ion mobility spectrometry detection (MIPF-SPME-IMS)

In this study, we use corona discharge ion mobility spectrometry (CD-IMS) as a detection technique for determining thidiazuron (TDZ) after its selective microextraction using molecularly imprinted polymer (MIP) fibers. This is the first time that MIP fiber solid phase microextraction-ion mobility spectrometry (MIPF-SPME-IMS) was used to detect TDZ. The fiber was synthesized simply using a narrow bore silica capillary as a mold by the copolymerization of methacrylic acid–ethylene glycol dimethacrylate imprinted with TDZ. The prepared MIPs were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM). The obtained flexible MIP monolithic fibers have high chemical and thermal stabilities with good selectivity to TDZ. The effective parameters influencing the polymerization were also investigated. In addition, the influences of different factors such as pH, extraction time, desorption solvent, and temperature on the extraction efficiency of the analyte were investigated. Under the optimum conditions, analytical parameters such as linearity, precision and limit of detection were also evaluated. The linear range was in the range of 0.01–20μgL−1 (r2=0.9980) and the limit of detection was 0.005μgL−1. Intra- and inter-day precisions were satisfactory with a relative standard deviation (RSD) of 0.9% and 2%, respectively. Finally, the established MIPF-SPME-IMS method was successfully applied in the selective determination of TDZ residues in fruit and vegetable samples.

Polymeric Colloidal Nanostructures Fabricated via Highly Controlled Convective Assembly and Their Use for Molecular Imprinting.

In this work, the formation of various polystyrene (PS) colloidal structures on striped PS patterns is demonstrated based on a simple and novel convective assembly method that controls the electrostatic interactions between the PS colloidal particles and sodium dodecyl sulfate (SDS). Under the optimal conditions (different withdrawal speeds, channel dimensions, suspension concentrations, etc.), highly ordered structures such as highly close-packed, zigzag, and linear colloidal aggregates are observed. In addition, these colloidal arrangements are used for development of molecularly imprinted polymer (MIP) sensors with highly improved sensing properties. Using PDMS replicas, three hemispherical poly(methacrylic acid-ethylene glycol dimethacrylate) (poly(MAA-EGDMA)) MIP films, including planar MIP and non-imprinted polymer (NIP) films, are photopolymerized for detection of trace atrazine in an aqueous solution. From gravimetric quartz crystal microbalance (QCM) measurements, a non-close-packed MIP film exhibits highest sensing response (Δf = 932 Hz) to atrazine detection among hemispherical MIP films and shows 6.5-fold higher sensing response than the planar MIP film. In addition, the sensitivity of the MIP sensor is equivalent to -119 Hz/(mol L(-1)). From the ratio of slopes of the calibration curves for the hemispherical MIP and NIP films, the imprinting factor (If) is as high as 11.0. The hemispherical MIP film also shows excellent selectivity in comparison with the sensing responses of other analogous herbicides. As a result, this molecular surface imprinting using PS colloidal arrays is highly efficient for herbicide detection.

The effect of crosslinking density on molecularly imprinted polymer morphology and recognition

In this report, the crosslinking density of bupivacaine molecularly imprinted methacrylic acid (MAA)–ethylene glycol dimethacrylate (EGDMA) copolymers was investigated through replacement of EGDMA by methyl methacrylate (MMA). The effects were examined using a series of full-scale MD simulations of pre-polymerization mixtures, equilibrium rebinding studies on the corresponding synthesized polymers and morphology characterization through nitrogen sorption measurements. While the extent of hydrogen bonding between the functional monomer MAA and bupivacaine observed in the MD pre-polymerization mixtures was comparable in each of the systems studied, the decrease in degree of crosslinking impacted directly on polymer morphology as observed in BET and BJH studies of surface area and porosity. Further, decreases in the crosslinking density induced reductions in template rebinding capacity as seen from a series of radio-ligand binding studies, demonstrating the importance of crosslinking on the performance of molecularly imprinted MAA–EGDMA copolymers, the polymer system most commonly used in molecular imprinting science and technology.

TiO₂ nanoparticles functionalized monolithic capillary microextraction online coupled with inductively coupled plasma mass spectrometry for the analysis of Gd ion and Gd-based contrast agents in human urine.

In this work, a novel method of TiO2 nanoparticles (NPs) functionalized monolithic capillary microextraction (CME) online coupling with inductively coupled plasma mass spectrometry (ICPMS) was developed for the sequential determination of Gd(3+) and Gd-based contrast agents in human urine samples. The monolithic capillary was prepared by embedding anatase TiO2 NPS in the poly(methacrylic acid-ethylene glycol dimethacrylate) (MAA-EDMA) framework. The Gd(3+) and Gd-based contrast agents (such as gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) and Gd-DTPA-bismethylamide (Gd-DTPA-BMA)) display different adsorption behaviors on the prepared monolithic capillary which possesses the adsorption properties of both anatase TiO2 NPS and poly(MAA-EDMA) monolith. Under the optimized conditions, the limits of detection (LODs) were found to be 3.6, 3.2, and 4.5 ng L(-1) for Gd(3+), Gd-DTPA, and Gd-DTPA-BMA, respectively, which are the lowest up to date. The enrichment factor was 25-fold with the sample throughput of 5 h(-1). The proposed method was validated by the analysis of Gd(3+) and Gd-DTPA in the healthy human urine samples as well as Gd(3+) and Gd-DTPA-BMA in patient urine samples. It was found that only a small amount of the free Gd(3+) was released from Gd-DTPA-BMA, and accurate results could be obtained since no oxidation/reduction or subtraction is involved in this method. This method is simple, sensitive, and rapid and provides a very attractive nonchromatography strategy for the speciation of Gd(3+) and Gd-based contrast agents in urine samples.

The development of methacrylic acid based monolithic discs used in the microfluidic chips for application in the determination of catecholamines

A solid phase extraction (SPE) based monolithic disc integrated microchip was developed for purposes of detection or qualitative determination of basic catecholamines: epinephrine (E), norepinephrine (NE) and dopamine (DA). The method is based on the use of a weak cation-exchange porous monolith, prepared in situ in the chamber of the boro-float microchip via photoinitiated polymerization to form desired poly(methacrylic acid-ethylene glycol dimethacrylate) [poly(MA-EGDMA)] monolithic phase which served as a SPE matrix. A surface area of 29.45m2g−1 was measured for the monolithic SPE material, obtained by using BET (Brunauer–Emmett–Teller) method. Adsorption of the catecholamines on SPE monolith was achieved using 20mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), buffered at pH 7 to protonate analytes while desorption was performed with 100mM phosphate, buffered at pH 3 to protonate the carboxylate groups of the monolithic phase which releases the analytes. The effects of the two sample injection methods (electrokinetic and pressure) on adsorption using cation-exchange based monolithic disc were examined. The detection of catecholamines was achieved on the separation channel of the microchip during the elution step via a laser-induced native fluorescence (LINF) measurement without any expensive and time consuming labelling processes. Different buffer combinations were used to establish a good correlation between native fluorescence intensity and high elution ratio of the catecholamines. The applicability of this approach to standard catecholamine solutions promises a potential for future investigations such as catecholamine separation and detection in actual samples.

Development of a solid‐phase microextraction fiber coated with poly(methacrylic acid‐ethylene glycol dimethacrylate) and its application for the determination of chlorophenols in water coupled with GC

A solid-phase microextraction (SPME) fiber coated with poly(methacrylic acid-ethylene glycol dimethacrylate) coupled to GC with a micro electron-capture detector was developed for the determination of four chlorphenols in water samples for the first time. A novel and simple method for the preparation of this novel SPME fiber was proposed by copolymerization of methacrylic acid and ethylene glycol dimethacrylate in an appropriate solvent using a glass capillary as a "mold". The factors affecting the polymerization were optimized in detail. Furthermore, the extraction performance of the poly(methacrylic acid-ethylene glycol dimethacrylate) fiber was evaluated. Moreover, experimental headspace-SPME parameters, such as extraction temperature, extraction time, salt concentration, stirring speed, and pH, were optimized by orthogonal array experimental designs. Under the optimized conditions, the target analytes were linear in the range of 0.2-50 ng/mL, and the correlation coefficients were all greater than 0.99. RSD was less than 8.9%, and the detection limits were in the range of 0.1-10 ng/L. Four cholorphenols were detected from tap and lake water samples using the proposed method, with the recoveries of spiked natural water samples were ranged from 91.8 to 110.8, and 90.6 to 111.4% for tap and lake water samples, respectively.

Hydrogel Containing Silica Shell Cross-Linked Micelles for Ocular Drug Delivery

Poly(2-hydroxyethyl methacrylate-methacrylic acid-ethylene glycol dimethacrylate) hydrogels loaded with silica shell cross-linked methoxy(polyethylene glycol)-block-polycaprolactone (MePEG-b-PCL) micelles with rod-like morphology were prepared as a potential soft contact lens material for the sustained release of ocular drugs. The silica shell cross-linked methoxy micelles (SSCMs) comprising a polycaprolactone core surrounded by a silica shell were synthesized and their size, morphology, stability, and drug release kinetics were evaluated. The relationships between the composition of the SSCM-loaded poly(2-hydroxyethyl methacrylate) (pHEMA)-based hydrogels and their transparency, surface wettability, and equilibrium water content were determined. Scanning electron microscopy (SEM) images of SSCM-hydrogel systems showed the presence of intact SSCMs within the hydrogel matrix. Dexamethasone acetate (DMSA), a hydrophobic ophthalmic drug, was loaded into the SSCMs prior to their incorporation into the hydrogels. In vitro release of DMSA from the SSCM-hydrogels, with varying drug loading levels, was observed for up to 30 days. Overall, the incorporation of rod-like SSCMs within pHEMA-based hydrogels provided sustained release over prolonged periods while maintaining optical transparency. This delivery system may be suitable for use as a therapeutic soft contact lens material.

Polymer Monolith Microextraction Coupled with HPLC for Determination of Jasmonates in Wintersweet Flowers

A simple, fast, and effective method has been presented for the determination of jasmonates in plant samples by polymer monolith microextraction (PMME). A poly (methacrylic acid-ethylene glycol dimethacrylate) (MAA-EGDMA) monolith-based device was developed for extraction, purification, and concentration; HPLC-UV was used for evaluation. To realize the best microextraction efficiency, parameters such as sample pH value, flow rate, and sample volume were systematically examined and optimized. Aqueous solution (5 mL) of jasmonates at pH 3.0 was selected as sample solution, and loaded onto the monolith at flow rate of 0.15 mL/min; finally, 50 μL of acetonitrile was used for elution. The proposed method exhibited impressive enrichment efficiency (almost 100-fold) and the limits of detection for jasmonic acid and methyl jasmonate obtained 0.5 and 2 ng/mL by using UV detection. Wide linear ranges were also observed (2–2000 and 5–2000 ng/mL) for both jasmonic acid and methyl jasmonate, with R2 > 0.999. The developed PMME-HPLC method was successfully applied to the determination of jasmonates in fresh wintersweet flowers with recoveries in the range of 91.9–97.2%. The result was confirmed by an HPLC-MS method. The PMME method was also compared with a conventional C18-SPE method and exhibited better clean-up efficiency.

Determination of sulfonamides in food samples by membrane-protected micro-solid phase extraction coupled with high performance liquid chromatography

In the present study, a simple and sensitive extraction method based on polypropylene membrane-protected micro-solid phase extraction (MP-μ-SPE) has been developed for analysis of sulfonamides in food samples. Poly (methacrylic acid-ethylene glycol dimethacrylate) (p-MAA-EDMA) was synthesized using orthogonal array experimental design, optimized with three factors at four levels and evaluated on yield, hydrophobic and cation-exchange properties. The optimized p-MAA-EDMA was then employed as the sorbent in the MP-μ-SPE for extraction of sulfonamides from milk and chicken muscle samples, followed by high performance liquid chromatographic analysis with ultraviolet detection. Under optimized extraction conditions, good linearities (0.010-1.0 μg mL(-1) with r(2)>0.9900), low limits of detection (0.38-0.62 ng mL(-1)), and acceptable intra-day (2.7-13.7%) and inter-day (6.7-15.2%) relative standard deviations were obtained. It was demonstrated to be an effective approach to handle semi-solid/solid samples with good resistance to interference from "dirty" samples.

Development of molecularly imprinted co-polymeric devices for controlled delivery of flufenamic acid using supercritical fluid technology

This work reports the development of a novel class of affinity co-polymeric materials using supercritical fluid technology. Polymeric materials with molecular recognition to flufenamic acid, were first synthesized in supercritical carbon dioxide (scCO 2) using the drug as template. Molecularly imprinted co-polymers of methacrylic acid (MAA) or N-isopropyl acrylamide (NIPAAm) crosslinked with ethylene glycol dimethacrylate (EGDMA) were synthesized using different crosslinking degrees and template:monomer ratios, at 65 °C and 21 MPa. High-pressure NMR experiments confirmed that the nature of the interactions between the drug and the functional monomers during the polymerization step are mainly hydrogen bonds. scCO 2-assisted impregnation revealed that the imprinted matrices were able to uptake higher amounts of flufenamic acid. This effect was particularly evidenced in the more crosslinked matrices, with P(MAA–EGDMA) imprinted copolymers binding up to 101.5 mg drug/g polymer against only 50.5 mg/g in the non-imprinted copolymer. In vitro drug delivery experiments showed that imprinted co-polymers release the drug in a more sustained way than the corresponding non-imprinted matrices. Overall it was shown that supercritical fluid technology is a viable approach for the development of self-assembly molecular recognition polymers with potential application in controlled drug delivery systems.

Dielectric enhancement in cadmium sulfide—poly(methacrylic acid-ethylene glycol dimethacrylic acid) nanocomposite through interfacial interaction

Dielectrical property on poly(methacrylic acid-ethylene glycol dimethacrylate) [P(MAA-EDMA)] attached with nanosized CdS particles have been studied. The attachment of CdS nanoparticles alters the dielectric property of CdS-P(MAA-EDMA) samples. By addition of a certain amount of CdS nanoparticles, the dielectric constant at room temperature and 100 Hz of the CdS-P(MAA-EDMA) is enhanced by ca. 500 times, which is attributed to the interfacial interaction of CdS nanoparticles with polymer surface. The large value of dielectric constant is due to interfacial space charge polarization.

Promethazine determination in plasma samples by using carbon paste electrode modified with molecularly imprinted polymer (MIP): Coupling of extraction, preconcentration and electrochemical determination

A promethazine (PMZ) molecularly imprinted polymer (MIP) and a non-imprinted polymer (NIP) were synthesized by two different formulations of methacrylic acid–ethylene glycol dimethacrylate (MAA–EGDMA) and vinyl benzene–divinyl benzene (VB–DVB). Then, the MIPs were used to modify the carbon paste electrode (CP). The response difference between MIP-CP and NIP-CP electrodes, containing VB–DVB polymer, was higher than that for MIP-CP and NIP-CP modified with polymer of MAA–EGDMA, indicating the lower nonselective surface adsorption property of the VB–DVB based MIP. The MIP, incorporated in the carbon paste electrode, functioned as selectively recognition element and pre-concentrator agent for PMZ determination. The prepared electrode was used for PMZ measurement by the three steps procedure including analyte extraction in the electrode, electrode washing and electrochemical measurement of PMZ. It was shown that the electrode washing, after PMZ extraction, led to enhanced selectivity. Square wave voltammetry (SWV) for PMZ determination by proposed electrode was proved to be better than that of differential pulse voltammetry. Some parameters, effective on the electrode response, were optimized and then a calibration curve was plotted. Two dynamic linear range of 7 × 10 −9 to 4 × 10 −7 and 4 × 10 −7 to 7 × 10 −6 mol L −1 were obtained. The detection limit of the method was calculated equal to 3.2 × 10 −9 mol L −1. This method was used successful for PMZ determination in blood serum sample.

A novel potentiometric sensor for promethazine based on a molecularly imprinted polymer (MIP): The role of MIP structure on the sensor performance

A novel potentiometric sensor based on a molecularly imprinted polymer (MIP) for determination of promethazine (PMZ) was prepared. Promethazine MIP particles were prepared and dispersed in 2-nitrophenyloctyl ether and then embedded in a polyvinyl chloride matrix. The effect of the monomers type on the sensor performance was investigated, and an important role for this parameter was shown. It was shown that the membrane electrode with a MIP prepared by vinylbenzene and divinylbenzene had a better performance in comparison to membrane electrodes containing MIPs prepared with methacrylic acid-ethylene glycol dimethacrylate or vinylbenzene-ethylene glycol dimethacrylate. After optimization, the membrane electrode constructed with a MIP of vinylbenzene-divinylbenzene exhibited a Nernstian response (31.2 ± 1.0 mV decade −1) over a wide concentration range, from 5.0 × 10 −7 to 1.0 × 10 −1 M, with a low detection limit of 1.0 × 10 −7 M and a response time of ∼50 s. The method has the requisite accuracy, sensitivity and precision to assay PMZ in syrup samples and biological fluids.

Evaluating polymer monolith in-tube solid-phase microextraction coupled to liquid chromatography/quadrupole time-of-flight mass spectrometry for reliable quantification and confirmation of quinolone antibacterials in edible animal food

A simple, rapid, and sensitive method is presented to determine seven trace quinolone antibacterials simultaneously in milk, egg, chicken and fish. This method is based on the combination of polymer monolith in-tube solid-phase microextraction with liquid chromatography and electrospray ionization quadrupole time-of-flight mass spectrometry (LC/ESI-QTOF-MS). LC/ESI-QTOF-MS offers the capability of unequivocal identification of target compounds from complex matrices, as well as the possibility of quantitation at low-level concentrations in real samples. The extraction was performed with a poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic column. Under the optimized extraction conditions, good extraction efficiencies for the targets were obtained with no matrix interference in the subsequent LC/ESI-QTOF-MS. Good linearities were obtained for seven quinolones with the correlation coefficients ( R) above 0.9951. The limits of detection ( S/ N = 3) for seven quinolones were found to be 0.3–1.2 ng/g in egg, 0.2–3.0 ng/mL in milk, 0.2–0.7 ng/g in chicken and 0.2–1.0 ng/g in fish. The recoveries of quinolones spiked in four different matrices ranged from 80.2 to 115.0%, with relative standard deviations less than 14.5%. The developed method was applied for the determination of quinolone residues in animal-producing food, and the positive samples were confirmed with high number of identification points (IPs) according to the IP system defined by the European Union (Commission Decision 2002/657/EC).

Monitoring of sulfonamide antibacterial residues in milk and egg by polymer monolith microextraction coupled to hydrophilic interaction chromatography/mass spectrometry

A simple, rapid, and sensitive method for the determination of traces of thirteen sulfonamide antibacterials in milk and eggs is presented. This method is based on the combination of polymer monolith microextraction (PMME) technique with hydrophilic interaction chromatography/mass spectrometry (HILIC/MS). The extraction was performed with a poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary column while the subsequent separation was carried out on a Luna NH 2 column by HILIC. To obtain optimum results, several parameters relating to HILIC and PMME were investigated. After optimization, acetonitrile (contain 0.05% formic acid, v/v) was used as the elution solution, which was well compatible with the mobile phase in HILIC. Good linearities were obtained for thirteen SAs with the correlation coefficients ( R 2) above 0.997. The limits of detection (S/N = 3) of the method were found to be 0.4–5.7 ng mL −1 of SAs in whole milk and 0.9–9.8 ng g −1 of SAs in eggs. The recoveries of thirteen SAs in two matrices ranged from 80.4 to 119.8%, with relative standard deviations less than 11.8%.