Presence Of Methylparaben Research Articles

Innovative UPLC technique for concurrent quantification of etofenamate and benzyl nicotinate in the presence of methylparaben and benzyl alcohol in their topical cream: Greens, white, and Six Sigma methodologies.

The efficacious treatment of muscle and joint pain relies heavily on etofenamate (ETO) and benzyl nicotinate (BN), which possess robust anti-inflammatory and pain-relieving properties when paired with methylparaben (MP) or benzyl alcohol (BA). In this study, we have established and validated innovative RP-UPLC methods for assessing ETO and BN in the presence of MP or BA in their dosage forms, employing eight green tools to evaluate their eco-friendliness and effectiveness. Reversed phase-ultra-performance liquid chromatography (RP-UPLC) technique employs a flow rate of 0.3mL/min on Waters Acquity UPLC BEH Column (C18, 1.7μm, 100 mm × 2.1mm), detection at 254 nm using a photo diode array (PDA) detector and mobile phase of 0.05 M KH2PO4 buffer, acetonitrile, and methanol (50:15:35, v/v/v) adjusted pH6.0 with 0.2% triethylamine. For ETO, BN, MP, and BA, the calibration curves were linear and ranged from 0.005 to 1.0, from 0.001 to 0.2, from 0.002 to 0.08, and from 0.0001 to 0.1mg/mL, respectively. The correlation value was 0.9999, and the accuracy findings ranged from 98.81% to 100.56%. Consequently, the methodology has been successfully implemented in assay testing for the pharmaceuticals in the presence of the MP or BA, demonstrating the high selectivity of these approaches. The present study presents the Blue Applicability Grade Index (BAGI), an innovative approach that complements green metrics in practical white analytical chemistry. According to the International Council for Harmonisation (ICH) criteria, the procedures were effectively validated.

Chitosan-Based Molecularly Imprinted Polymer Modified Zinc Oxyde/Graphene Nanocomposite/Screen Printed Carbon Electrode for Electrochemical Detection of Methyl Paraben

A novel electrochemical sensor, chitosan based on molecularly imprinted polymer (MIP), was fabricated by electrodeposition of chitosan in the presence of methyl paraben (MP) on a zinc oxide/graphene nanocomposite (ZnO/GnC) modified screen-printed carbon electrode for selective detection of MP. The obtained chitosan-based MIP modified electrode, namely MIP/ZnO/GnC/SPCE was characterized by scanning electron microscopy, cyclic voltammetry, and differential pulse voltammetry. Under the optimized condition, the prepared sensor MIP/ZnO/GnC/SPCE exhibited satisfactory linearity with certain MP concentrations of 10 to 1000 μM and the limit of detection can reach 9.65 μM with a sensitivity of 0.00445 μA/μM.cm2. This work shows that the incorporation of chitosan-based MIP with ZnO/GnC generates a synergistic effect, increasing the current response in comparison with unmodified SPCE. The developed sensor exhibited satisfactory reproducibility and repeatability. Furthermore, the developed electrode was successfully applied for the determination of MP in cosmetic products and shows similar performance in comparison to UV-visible spectrophotometry analysis. In conclusion, the chitosan-based MIP modified ZnO/GnC/SPCE is promising for monitoring the MP in cosmetic products.

Presence of methyl paraben in anti-diabetic herbal preparations

Plant-based hypoglycemic therapeutics have been increasing in consumption due to the escalation of type 2 diabetes and its related complications. However, the safety of the preparations is little understood. Parabens (alkyl esters of p-hydroxybenzoic acid) are widely used as preservatives in these pharmaceuticals. However, the presence of methylparaben in formulations raises anxiety due to its potential endocrine disruption functions. Endocrine disruption could lead to undesirable health abnormalities and carcinogenic, estrogenic, and adverse reproductive effects. The present investigation directs toward estimating of methylparaben in some anti-diabetic herbal preparations using UV- Vis spectrophotometric method abiding by International Conference on Harmonization (ICH) guidelines for validation. The analytical wavelength of methylparaben in methanol was determined and found at 256.5 nm. The method obeys Beer’s law in the analytical range and has a good coefficient of determination (r2= 0.9881). The limit of detection (LOD) and limit of quantification (LOQ) were 0.19 ppm and 0.57 ppm, respectively. Recoveries were 91.3-98.8% in analyte-free plant matrix and 91-105.8 % in a diluent. The coefficient of variation (CV%) varied between 0.005- 0.268% for different standards. Results of forty-eight anti-diabetic herbal preparations showed methylparaben was detected in thirty-four samples in the range of 13.12 – 325.13 mg/day with a mean exposure value of 78.25 mg/day. However, none of the samples raise concerns about safety (the safety ceiling for paraben is 420 mg/day). More investigation is required to determine, whether the herbal drugs are safe to consume in terms of methylparaben. J. Asiat. Soc. Bangladesh, Sci. 48(1-2): 41-52, June-December 2022

A new simple liquid chromatographic assay for gentamicin in presence of methylparaben and propylparaben

AbstractGentamicin sulfate is a potent broad spectrum aminoglycoside antibiotic which is used against Gram-positive and Gram-negative bacteria. A simple, isocratic HPLC method for separation, identification and determination of gentamicin and parabens (methylparaben and propylparaben) was developed and validated. To our knowledge there is no report about simultaneous determination of those three analytes in pharmaceutical products. The optimum chromatographic conditions were achieved on CN column with a mobile phase consisting of 0.15% triethylamine in 10 mM KH2PO4 aqueous solution (final pH 3.0 adjusted with H3PO4) and methanol in the ratio 70:30 (v/v), providing selective quantification of analytes within 5 min. The method was successfully validated according to ICH guidelines acceptance criteria in terms of selectivity, linearity, accuracy, precision and robustness. The linearity of the method was proved in defined concentrations ranges for gentamicin (0.32–1.04 mg mL−1), methylparaben (0.0072–0.0234 mg mL−1) and propylparaben (0.0008–0.0026 mg mL−1). Relative standard deviations calculated for all analytes in precision testing were <2% (analysis repeatability) and <3% (intermediate precision). Recovery values were between 98.87% and 101.67%. Chromatographic parameters are not significantly influenced by small variations of column temperature, pH and molarity of KH2PO4. Finally, the method was successfully applied for quantitative determination of gentamicin and parabens in commercially available solution for injection. Proposed HPLC method is found to be promising in terms of simplicity, analysis times and non-use of derivatization and ion-pair agents.

Synergistic Adsorption of Organic Pollutants on Weathered Polyethylene Microplastics.

Microplastics (MPs) are persistent tiny pieces of plastic material in the environment that are capable of adsorbing environmental organic pollutants from their surroundings. The interaction of MPs with organic pollutants alters their environmental behavior, i.e., their adsorption, degradation and toxicity, etc. Polyethylene (PE) is the most widely used plastic material. The environmental weathering of PE results in changes to its surface chemistry, making the polymer a much better vector for organic pollutants than virgin PE. In this study, a laboratory-accelerated weathering experiment was carried out with a virgin PE film and an oxidatively degradable PE (OXO-PE) film, i.e., PE modified by the addition of a pro-oxidant catalyst. The degradation of PE and OXO-PE was assessed through Fourier transform infra-red (FTIR) spectroscopy and their wettability was measured by contact angle (CA) measurements. Their thermal properties and morphology were studied using thermogravimetric analyses (TGA) and scanning electron microscopy (SEM), respectively. Further, the adsorption of two model organic pollutants onto weathered and virgin PE was analyzed. Triclosan (TCS) and methylparaben (MeP) were chosen as model organic pollutants for the adsorption experiment due to their frequent use in the cosmetics industry, their uncontrolled release into the environment and their toxicity. The adsorption of both model pollutants onto PE and OXO-PE MP was analyzed by using gas chromatography with a flame ionization detector (GC-FID). The adsorption of MeP onto OXO-PE was higher than onto PE MPs. However, TCS showed insignificant adsorption onto PE and OXO-PE. When both pollutants were present simultaneously, the adsorption of TCS onto both PE and OXO-PE was significantly influenced by the presence of MeP. This result demonstrates that the adsorption behavior of one pollutant can be significantly altered by the presence of another pollutant. Both the effect of weathering on the adsorption of organic pollutants as well as the interaction between organic pollutants adsorbing onto MPs is highly relevant to actual MP pollution in the environment, where MPs are exposed to weathering conditions and mixtures of organic pollutants.

Validated Smart Different Chromatographic Methods for Selective Quantification of Acefylline Piperazine, Phenobarbital Sodium and Methylparaben Additive in Bulk and Pharmaceutical Dosage Form.

Two chromatographic methods have been proposed for the simultaneous determination of acefylline piperazine (ACEF) and phenobarbital (PHENO) in presence of methylparaben as additive in pharmaceutical dosage form. The first method was thin-layer chromatography. The separation was achieved using silica gel as stationary phase and chloroform: methanol: glacial acetic acid (2.0, 8.0 and 0.1, by volume) as a developing system at 254nm. Accurate determination of both drugs was attained over the concentration range of 0.5-25μg/band. The second method was based on the use of reversed phase liquid chromatography with diode array detection, by which the proposed components were separated on a reversed phase C18 analytical column using methanol: water (60: 40, by volume) as a mobile phase with flow rate of 0.8mL/min at 214nm in a concentration range of 0.5-100μg/mL. The proposed chromatographic methods were practiced successfully for the determination of ACEF and PHENO in pharmaceutical dosage form. Both methods were validated according to the International Conference on Harmonization guidelines and statistically compared with a reported high-performance liquid chromatograph method. Planar chromatography has never been proposed in the literature for ACEF and PHENO determination besides the proposed columnar chromatographic method using an isocratic eco-friendly mobile phase.

Electrochemical degradation of a methyl paraben and propylene glycol mixture: Interference effect of competitive oxidation and pH stability

Endocrine disrupting compounds (EDCs) are one of the many classes of harmful pollutants frequently found in water resources. Even at low concentrations, EDCs might accumulate in the organisms and interfere on numerous processes controlled by hormones. Parabens, for example, are preservatives widely used in pharmaceutical and cosmetic industries, but several studies related them to human breast cancer. It is well-known that electrochemical technologies are an efficient alternative for wastewater treatment, promoting the appropriate destruction of EDCs. However, most studies are applied to single target contaminant solutions, which may neglect the impact from co-exited inorganic/organic pollutants. Based on that, this study aimed to elucidate the interfering effects of two target organic contaminants of very different nature during electrochemical mediated process. For that, methyl paraben (MeP) and propylene glycol (PG) were selected as models of aromatic/phenolic and carboxylate compounds versus low-molecular aliphatic alcohols. These two compounds are often together used in preservative blends and cosmetic/pharmaceutical formulations. PG is not a harmful chemical, but it is present in several types of effluents in relatively high concentrations. Thus, it may interfere on the degradation of numerous pollutants of low concentrations. The electrochemical treatment of a mixture containing 100 mg L−1 MeP +1000 mg L−1 PG showed that both contaminants suffered interfering effects. The presence of MeP negatively interfered on PG degradation; the carboxylate compound is more easily oxidized even at lower molecular concentration. On the other hand, the presence of PG showed an unexpected positive effect on MeP degradation, that was not reflected on its mineralization. The results indicate that in addition to the expected effect of anodic competition, polymerization and copolymerization reactions may also occur in the studied system. The use of an acidic buffer medium increased the removal of both contaminants and favored the oxidation pathway over the polymerization. In this case, the increase in the removal was reflected in the mineralization process, which increased up to 6 times when the mixture was treated in the buffered medium.

Urinary Paraben Concentration and Its Association with Serum Triglyceride Concentration in 2013-2014 NHANES Participants: A Cross-Sectional Study

Background Alkyl esters of para-hydroxybenzoic acid, colloquially known as parabens, are types of preservatives found in multiple foodstuffs, pharmaceuticals, and personal care products to which Americans are exposed daily. It is unclear if parabens exhibit endocrine-disrupting properties. Parabens may interact with triglycerides in adipose tissue and impact lipid metabolism. Objective To evaluate the association between urinary paraben concentrations and serum triglyceride concentrations. Design A cross-sectional study. Setting. The Mobile Examination Centers affiliated with 2013-2014 NHANES. Participant(s). 827 adults (20 years or older) affiliated with the 2013-2014 NHANES. Intervention(s). None. Main Outcome Measure(s). Triglyceride levels were associated with urinary paraben concentrations (methyl, ethyl, and propyl) using a hierarchical multiple regression, adjusting for ethnicity/race, gender, BMI, and age. Unadjusted results are also reported. Results The geometric mean of the urinary concentration of methylparaben, ethylparaben, and propylparaben was 57.100, 2.537, and 6.537 ng/ml, respectively. Triglyceride concentrations were inversely associated with methylparaben (β = −0.092, P=0.07), ethylparaben (β = −0.066, P=0.045), and propylparaben (β = −0.076, P=0.025). Being female, non-Hispanic White, and non-Hispanic Black were associated with decreasing triglyceride levels in the presence of methylparaben, ethylparaben, and propylparaben, and age, BMI, and being male were associated with increasing circulating triglycerides. Conclusion Despite the potential detrimental effects of parabens on triglycerides, our results suggest that urinary excretions of methylparaben, ethylparaben, and propylparaben are associated with lower concentrations of circulating triglycerides in certain populations. Further research is needed to confirm the mechanisms and health impact of this relationship.

Green validated HPTLC and HPLC methods for determination of ephedrine hydrochloride and naphazoline nitrate in the presence of methylparaben, in their pure forms and pharmaceutical formulation

Green validated high-performance thin-layer chromatography (HPTLC) and high-performance liquid chromatography (HPLC) methods were established for resolving ephedrine hydrochloride (EPH), naphazoline nitrate (NAP), and methylparaben (MET) mixture. Method A is HPTLC–densitometric one that depends on their separation and quantitation on HPTLC silica gel 60 F254 plates, using ethyl acetate:ethanol:triethylamine (8:2:0.2, v/v) as a developing system followed by densitometric measurement at 220 nm. Method B includes HPLC separation and quantification of the introduced mixture on C18 column using a mobile phase consisting of water:ethanol:acetonitrile (80:20:2, v/v) flowing at 1 mL/min. The separated peaks were detected at 220 nm. International Conference on Harmonization (ICH) guidance for method validation was obeyed; EPH and NAP can be determined in the concentration ranges of 2–16 μg/band and 0.4–1.8 μg/band, respectively, using HPTLC method and 5–30 μg/mL and 2–30 μg/mL, respectively, using HPLC method with correlation coefficients > 0.9995. The methods were proven to be accurate, selective, and repeatable for the determination of the two drugs, and can be used for their estimation to check their purity in powder forms and quantifying them in pharmaceutical formulation. The greenness of the procedures was assessed to make sure that they have no adverse environmental effects.

Phototoxic assessment of a sunscreen formulation and its excipients: An in vivo and in vitro study

BackgroundCosmetic preservatives are used to protect cosmetic formulations and improve its shelf-life. However, these substances may exert phototoxic effects when used under sunlight. ObjectiveTo assess safety, efficacy and putative phototoxic effects of a sunscreen formulation SPF 30 and its excipients. Materials/MethodsIrradiation was performed with solar simulated light (SSL) and the sunscreen from the School of Pharmacy/UFRJ/Brazil. We used albino hairless mice in different groups (control (G1), only irradiated (G2), sunscreen plus irradiation (G3) and vehicle plus irradiation (G4) for morphological assessment and immunefluorescence detection to OKL38. In vitro analyses were with a Saccharomyces cerevisiae (SC) strain plus SSL in the presence of methylparaben, propylparaben, imidazolidinyl urea, aminomethyl propanol and their association. ResultsG3 and G4 displayed photosensitization leading to thickening of the epidermis and increased dermal cellularity. G4 displayed strong OKL38 labeling when compared with other groups. Aminomethyl propanol, methylparaben and propylparaben are endowed with phototoxic activity against SC. Propylparaben displayed the highest phototoxic effect, followed by excipients association. ConclusionsThe sunscreen's vehicle is endowed with phototoxic activity. Propylparaben was the most phototoxic agent, increasing the overall phototoxicity of excipient association, pointing to a critical concern regarding vehicle associations intended to cosmetic purposes.

TLC-Densitometric and RP-HPLC Methods for Simultaneous Determination of Dexamethasone and Chlorpheniramine Maleate in the Presence of Methylparaben and Propylparaben.

Validated simple, sensitive, and highly selective methods are applied for the quantitative determination of dexamethasone and chlorpheniramine maleate in the presence of their reported preservatives (methylparaben and propylparaben), whether in pure forms or in pharmaceutical formulation. TLC is the first method, in which dexamethasone, chlorpheniramine maleate, methylparaben, and propylparaben are separated on silica gel TLC F254 plates using hexane-acetone-ammonia (5.5 + 4.5 + 0.5, v/v/v) as the developing phase. Separated bands are scanned at 254 nm over a concentration range of 0.1-1.7 and 0.4-2.8 μg/band, with mean ± SD recoveries of 99.12 ± 0.964 and 100.14 ± 0.962%, for dexamethasone and chlorpheniramine maleate, respectively. Reversed-phase HPLC is the second method, in which a mixture of dexamethasone and chlorpheniramine maleate, methylparaben, and propylparaben is separated on a reversed-phase silica C18 (5 μm particle size, 250 mm, 4.6 mm id) column using 0.1 M ammonium acetate buffer-acetonitrile (60 + 40, v/v, pH 3) as the mobile phase. The drugs were detected at 220 nm over a concentration range of 5-50 μg/mL, 2-90 μg/mL, 4-100 μg/mL, and 7-50 μg/mL, with mean ± SD recoveries of 100.85 ± 0.905, 99.67 ± 1.281, 100.20 ± 0.906, and 99.81 ± 0.954%, for dexamethasone, chlorpheniramine maleate, methylparaben paraben, and propylparaben, respectively. The advantages of the suggested methods over previously reported methods are the ability to detect lower concentrations of the main drugs and to show better resolution of interfering preservatives; hence, these methods could be more reliable for routine QC analyses.

Investigation into the interaction of methylparaben and erythromycin with human serum albumin using multispectroscopic methods.

In this paper, the interaction of methylparaben and erythromycin with human serum albumin (HSA) was studied for the first time using spectroscopic methods including Fourier transform infrared (FTIR) spectroscopy and UV absorption spectroscopy in combination with fluorescence quenching under physiological conditions. The binding parameters were evaluated using a fluorescence quenching method. Based on Förster's theory of non-radiation energy transfer, the binding average distance, r between the donor (HSA) and the acceptor (methylparaben and erythromycin) was evaluated. UV/vis absorption, FTIR, synchronous and 3D spectral results showed that the conformation of HSA was changed in the presence of methylparaben and erythromycin. The thermodynamic parameters were calculated according to the van't Hoff equation and are discussed. The effect of some biological metal ions and site probes on the binding of methylparaben and erythromycin to HSA were further examined.

Micellar liquid chromatographic determination of salbutamol sulfate in presence of methyl paraben, propyl paraben and benzoic acid: application to content uniformity testing

A micellar liquid chromatographic method was developed for the determination of salbutamol sulfate in presence of methyl paraben, propyl paraben and benzoic acid (syrup additives) using C8 column and mobile phase consisting of water (containing 0.1 % sodium dodecyl sulfate, 0.1 % glacial acetic acid and 0.1 % triethylamine, pH = 3.45):acetonitrile (55:45, v/v) with PDA detection at 220 nm at a flow rate 1 mL/min. Under these conditions, separation of the four components was achieved in less than 9 min. Analytical characteristics such as limit of detection, limit of quantitation, linearity range, accuracy, precision and the influence of the various method parameters (robustness study) were evaluated. The method was validated over the concentration range 1–50 μg/mL of salbutamol sulfate. Statistical analysis between the suggested method and the official HPLC method using Student’s t and F-ratio tests reveals that the suggested method is as accurate and precise as the official one.

Spectral characterization of the binding and conformational changes of bovine serum albumin upon interaction with an anti-fungal drug, methylparaben

The binding of methylparaben with bovine serum albumin (BSA) was investigated by spectroscopic methods viz., fluorescence, FT-IR and UV–vis absorption techniques under physiological conditions i.e., pH 7.4. Spectroscopic analysis of the emission quenching at different temperatures revealed that the quenching mechanism of bovine serum albumin by methylparaben shows a dynamic quenching. The binding sites number n and binding constants, K were obtained at various temperatures. The distance, r between methylparaben and BSA was evaluated according to the theory of Förster energy transfer. The result of FT-IR spectra and UV–vis absorption spectra showed that the conformation of bovine serum albumin has been changed in the presence of methylparaben. The thermodynamic parameters, enthalpy change (ΔH0) and entropy change (ΔS0) were calculated according to van’t Hoff equation, which indicated that the hydrophobic interaction was the predominant intermolecular force stabilizing the complex. The effect of common ions and site probes were also carried on the binding of methylparaben to BSA.

Methylparaben concentration in commercial Brazilian local anesthetics solutions

ObjectiveTo detect the presence and concentration of methylparaben in cartridges of commercial Brazilian local anesthetics.Material and methodsTwelve commercial brands (4 in glass and 8 in plastic cartridges) of local anesthetic solutions for use in dentistry were purchased from the Brazilian market and analyzed. Different lots of the commercial brands were obtained in different Brazilian cities (Piracicaba, Campinas and São Paulo). Separation was performed using high performance liquid chromatography (HPLC) with UV-Vis detector. The mobile phase used was acetonitrile:water (75:25 - v/v), pH 4.5, adjusted with acetic acid at a flow rate of 1.0 ml.min-1. ResultsWhen detected in the solutions, the methylparaben concentration ranged from 0.01% (m/v) to 0.16% (m/v). One glass and all plastic cartridges presented methylparaben. Conclusion1. Methylparaben concentration varied among solutions from different manufacturers, and it was not indicated in the drug package inserts; 2. Since the presence of methylparaben in dental anesthetics is not regulated by the Brazilian National Health Surveillance Agency (ANVISA) and this substance could cause allergic reactions, it is important to alert dentists about its possible presence.

Development and Application of Ultra Performance Liquid Chromatography Method to the Quantification of the Biotransformation of Methyl Paraben in Eisenia foetida

AbstractA simple and quick ultra performance liquid chromatography method (UPLC) has been developed for determination of methyl paraben (MP) and its major metabolites p‐hydroxybenzoic acid (pHBA) and phenol (Phe), following its biotransformations in Eisenia foetida. After different exposure time to paper contact test, the presence of methyl paraben and his biotransformation products in adult earthworms was monitored. Determination of its metabolites was achieved with a BEH (bridged ethane‐silicon hybrid) C18 column (2.1×50 mm i.d., 1.7 µm particle size), using methanol/water/phosphoric acid as mobile phase, under a gradient elution program, and a PDA (photo‐diode array) detection (quantification with MaxPlot in the range 210–400 nm). The absorption of MP did not exceed 30% and in the first 4–6 h after exposure only minute amounts of pHBA and Phe were detected in the worm homogenates. After 48 h of exposures, almost 70% of absorbed MP was already metabolized to Phe and around 20% could be found as pHBA.

Simultaneous Determination of Phenylephrine Hydrochloride, Guaifenesin, and Chlorpheniramine Maleate in Cough Syrup by Gradient Liquid Chromatography

A simple and reliable high-performance liquid chromatographic method was developed for the simultaneous determination of mixture of phenylephrine hydrochloride (PHENYL), guaifenesin (GUAIF), and chlorpheniramine maleate (CHLO) either in pure form or in the presence of methylparaben and propylparaben in a commercial cough syrup dosage form. Separation was achieved on a C8 column using 0.005 M heptane sulfonic acid sodium salt (pH 3.4 +/- 0.1) and acetonitrile as a mobile phase by gradient elution at different flow rates, and detection was done spectrophotometrically at 210 nm. A linear relationship in the range of 30-180, 120-1800, and 10-60 microg/mL was obtained for PHENYL, GUAIF, and CHLO, respectively. The results were statistically analyzed and compared with those obtained by applying the British Pharmacopoeia (2002) method and showed that the proposed method is precise, accurate, and can be easily applied for the determination of the drugs under investigation in pure form and in cough syrup formulations.

Development of a multidose formulation for a humanized monoclonal antibody using experimental design techniques.

The purpose of this study was to identify optimal preservatives for a multidose formulation of a humanized monoclonal antibody using experimental design techniques. The effect of antimicrobial parenteral preservatives (benzyl alcohol, chlorobutanol, methylparaben, propylparaben, phenol, and m-cresol) on protein stability was assessed using size-exclusion chromatography, differential scanning calorimetry, right-angle light scattering, UV spectroscopy, and potency testing using a cell-based fluorescence-activated cell sorting method. A quick, cost-effective preservative screening test was designed. Combinations of preservatives were examined using an I-optimal experimental design. The protein was most stable in the presence of methylparaben and propylparaben, and was compatible with benzyl alcohol and chlorobutanol at low concentrations. Phenol and m-cresol were not compatible with the protein. The I-optimal experimental design indicated that as an individual preservative, benzyl alcohol was promising. The model also indicated several effective combinations of preservatives that satisfied the antimicrobial efficacy and physical stability constraints. The preservative screening test and the experimental design approach were effective in identifying optimal concentrations of antimicrobial preservatives for a multidose protein formulation; (1) benzyl alcohol, and (2) the combination of methylparaben and chlorobutanol were screened as potential candidates to satisfy the regulatory requirements of various preservative efficacy tests.

Derivative spectrophotometric determination of droperidol in presence of parabens

We have developed a fast and accurate method for the determination of droperidol in the presence of methylparaben and propylparaben using derivative spectrophotometry. The first derivative amplitudes at 255.2 nm were selected for the assay. Calibration graph follows Beer's law in the range of 5–35 μg ml −1. The coefficient of variation (CV) for intra-day and inter-day precision were less than 1.0 and 2.0%, respectively. The method was applied in the quality control of commercial oral and injection solutions and proved to be suitable for routine analysis.

Zero-crossing derivative spectrophotometry for the determination of haloperidol in presence of parabens

First derivative spectrophotometry with a zero-crossing technique of measurement is used for the quantitative determination of haloperidol in the presence of methylparaben and propylparaben, which is added as antimicrobial preservatives in pharmaceuticals. This technique permits the quantification of haloperidol in the presence of parabens, with closely overlapping spectral bands, and without any separation step. Linear calibration graphs of first derivative values (at 255.2 nm for haloperidol) versus concentration (in the range 4.0–20.0 μg ml −1) were obtained with negligible intercepts. Relative standard deviation of 0.83% was obtained for intra-day precision and 1.86% for inter-day precision. The recovery of haloperidol in synthetic mixtures with parabens and in pharmaceutical dosage forms is also reported.