Ginseng root extract-mediated synthesis of monodisperse silver nanoparticles as a fluorescent probe for the spectrofluorometric determination of nilvadipine; Evaluation of remarkable anti-bacterial, anti-fungal and in-vitro cytotoxic activities.

Nanoparticles are a boon for humanity because of their improved functionality and unlimited potential applications. Considering this significance, the proposed study introduced a simple, fast and eco-friendly method for synthesis of fluorescent silver nanoparticles (Ag-NPs) using Panax Ginseng root extract as a reducing and capping agent. Synthesis of Ag-NPs was performed in one step within three minutes utilizing microwave irradiation. The resulting Ag-NPs were characterized using various microscopic and spectroscopic techniques such as, Transmission Electron Microscope (TEM), UV/Visible spectroscopy, Fourier Transform Infrared Spectroscopy(FTIR) and Energy Dispersive X-ray analysis (EDX). The prepared Ag-NPs, which act as a fluorescent nano-probe with an emission band at 416 nm after excitation at 331 nm, were used to assay nilvadipine (NLV) spectrofluorimetrically in its pharmaceutical dosage form with good sensitivity and reproducibility. The proposed study is based on the ability of NLV to quantitatively quench the native Ag-NPs fluorescence, forming a ground state complex as a result of static quenching and an inner filter mechanism. The suggested approach displayed a satisfactory linear relationship throughout a concentration range of 5.0 µM - 100.0 µM, with LOD and LOQ values of 1.18 µM and 3.57 µM, respectively. Validation of the suggested approach was examined in accordance with ICH recommendations. In addition, the anti-bacterial and anti-fungal activities of the prepared nanoparticles were investigated, and they demonstrated effective anti-microbial activities and opened a future prospective to combat future antibiotic resistance. Finally, in-vitro cytotoxicity assay of Ag-NPs against normal and cancerous human cell lines was studied using MTT assay. The results proved the potential use of the produced Ag-NPs as an adjunct to anticancer treatment or for drug delivery without significantly harming healthy human cells.

Microwave assisted synthesis of fluorescent hetero atom doped carbon dots for determination of betrixaban with greenness evaluation.

A simple, rapid and eco-friendly method for synthesis of nitrogen and sulfur doped carbon dots (N,S-CDs) is described. The method involved one step carbonization assisted by a green microwave irradiation route using available and cheap sources, as sucrose (source for C) and thiourea (source for N and S). The formed aqueous solution of N,S-CDs showed excellent optical and electronic properties with high compatibility and stability. The particles of the prepared dots were spherical with a narrow range of size from 1.7 to 3.7 nm with a quantum yield of 0.20. These dots act as a fluorescent probe, as they showed an intense blue fluorescence at 413 nm after excitation at 330 nm. The N,S-CDs were utilized for determination of the anticoagulant drug, betrixaban maleate (BTM), based on quenching of their fluorescence upon its gradual addition. The quenching process was found to be through an inner filter effect mechanism. The proposed method showed a good linearity over a concentration range of (1.0-100.0 µM) with LOD and LOQ values of 0.33 µM and 0.99 µM, respectively. All validation parameters met the acceptance criteria according to ICH guidelines. The high specificity and sensitivity of the performed method contributed to further assay of BTM in dosage form and spiked human plasma sample with high percent recoveries and low values of RSD. Interference from co-administered drugs was studied. Finally, the greenness of the proposed method was evaluated adopting a ComplexGapi approach, the excellent green profile has supported its applicability in quality control laboratories.

Investigating the Effect of Silver Nanoparticles on the Fluorescence Intensity of Bambuterol and its Active Metabolite Terbutaline Using FRET.

Silver nanoparticles (AgNPs) were found to significantly quench the fluorescence of bambuterol hydrochloride (BAM) and its active metabolite terbutaline sulfate (TER). The intrinsic fluorescence intensity of each of BAM (at 264/292 nm) and TER (at 276/306 nm) decreased by the gradual addition of AgNPs. Quenching of the steady state fluorescence of BAM and TER probably resulted from the energy transfer to the photo-excited state of AgNPs. The estimated Stern-Volmer quenching constant at several temperature settings proved that the quenching mechanism of the two drugs was dynamic quenching in case of BAM while it was static quenching in case of TER. The number of binding sites, binding constants, and corresponding thermodynamic parameters depending on the interaction system were estimated at 293, 313, and 333 °K and the results obtained were interpreted.

Insights for applying N,S-doped carbon dots as a fluorescent nanoprobe for estimation of some nitro-calcium channel blockers.

A facile and simple one-step hydrothermal approach was adopted for fabrication of N and S co-doped carbon quantum dots probe (NSCDs) by using thiosemicarbazide as a dopant and citric acid as a precursor. The prepared NSCDs with a high quantum yield of 0.58 were characterized using UV-visible spectroscopy, IR spectroscopy and high-resolution transmission electron microscopy. The as-obtained NSCDs could be deemed as an effective fluorescent nanosensor for the determination of some anti-hypertensive nitro-calcium channel blockers (Nitro-CCBs) including nicardipine (NIC), nifedipine (NIF) and nimodipine (NIM) whether in pure form or in their pharmaceutical formulations. Measurements of NSCD emission intensity were performed at 416 nm after being excited at 345 nm. Nitro-CCBs could induce quenching in the native fluorescence of NSCDs due to the inner filter effect and static quenching mechanism. The studied compounds were investigated within linear detection range of (10.0-100.0 µM) for NIC, (5.0-60.0 µM) for NIF and (5.0-60.0 µM) for NIM. Correlation coefficients are greater than or equal to 0.9998 and detection limits are ranged between 0.55 and 1.86 µM. The proposed method was extended to estimate the studied compounds in different pharmaceutical samples with high % recoveries ranging from (97.95 to 101.28%) and low % relative standard deviation values (less than 2%). Validation of the developed spectrofluorimetric method was done along with the International Council of Harmonization requirements.

Spectrofluorometric determination of residual amounts of nitroxynil in food samples.

Because of the frequent treatment of dairy cows with nitroxynil (NTX), the presence of the later residues in animal tissues and milk has a significant concern. The quantum yield of the reaction product was calculated. A highly sensitive and rapid spectrofluorometric method for determining the anthelmintic drug (NTX) residual amounts is developed. The proposed approach is based on using Zn/HCl to reduce NTX nitro group to an amino group, resulting in a highly fluorescent derivative that was detected at each of λem 302 nm and 364 nm after excitation at λex = 277 nm. The experimental conditions were carefully studied and optimized. The proposed approach showed good linearity (r2 ≥ 0.9998) with linearity range of 10.0-100.0 ng/mL with a detection limit of 1.89 ng/mL, 1.27 ng/mL and quantification limit of 5.73 ng/mL, 3.86 ng/mL at λem 302 nm and 364 nm, respectively; that is far below the Minimum Regulatory Limits (MRLs) of NTX in animal tissues and milk. The proposed approach was successfully applied for the analysis of the drug in its veterinary formulations, and the obtained results agreed well with those of the official British Pharmacopeia method. Moreover, the proposed method's application was extended to efficiently determine the residues of nitroxynil in meat, liver, kidney and milk samples.

Turn-off fluorescence of nitrogen and sulfur carbon quantum dots as effective fluorescent probes for determination of imatinib. Application to biological fluids.

Nitrogen and sulfur carbon quantum dots(N,S-CQDs) as effective fluorescent nanoprobes were synthesized through one-step-hydrothermal method using thiosemicarbazide (as nitrogen and sulfur source) and citric acid (as carbon source). The highly fluorescent N,S-CQDs were subjected to various characterization techniques. The fluorescence of the synthesized N,S-CQDs is characterized by maximum fluorescence emission at 415 nm after excitation at 345 nm and a high quantum yield of 0.58. The native N,S-CQDs fluorescence is quantitatively quenched upon addition of imatinib (IMA), so they are used for its spectrofluorimetric determination in its pharmaceutical formulations and biological fluids. Under optimal conditions, N,S-CQDs exhibited a "turn-off" fluorescence response to IMA over the range of 1.0 to 15.0 µg/mL with a limit of quantification of 0.42 µg/mL and a lower detection limit of 0.14 µg/mL. Stern-Volmer equation was used to study the mechanism of quenching and it was found to occur through static quenching mechanism. The method was extended to the in-vitro determination of the drug in spiked human urine and plasma samples and the percent recoveries were satisfactory.

Synchronized spectrofluorimetric determination of ponatinib and curcumin as an effective therapeutic combination in laboratory prepared mixtures and human plasma samples.

Curcumin is a natural product that is frequently utilized in cancer prevention and treatment. The significant benefit of vegetable-derived nutraceuticals in combination with widespread cytostatic medication such as ponatinib is to reduce toxicity and side effects. In this paper, we focus the study on analytical quantification of ponatinib and curcumin through highly sensitive synchronous spectrofluorometric method. Applying this method at Δλ = 160 nm, each of ponatinib and curcumin could be measured at 303 and 412 nm without interference from each others. The diverse experimental factors impacting the performance of the method were studied and optimized. The method exhibited a reasonable linearity in the ranges of 5.0-60.0 and 10.0-200.0 ng/mL for ponatinib and curcumin, respectively with detection limits of 1.48 and 1.22 ng/mL and quantitation limits of 4.49 and 3.68 ng/mL, respectively. The anticipated method was employed for the assessment and evaluation of the studied drugs in the spiked human plasma samples. The mean % recoveries in plasma samples (n = 6) for each of ponatinib and curcumin were 99.84 ± 1.86 and 100.06 ± 2.72, accordingly. The developed method was validated in conformity with the requirements of International Council of Harmonization (ICH).

Eco-friendly fluorimetric approaches for the simultaneous estimation of the co-administered ternary mixture: etoposide, moxifloxacin and nalbuphine.

Antineoplastic drugs, etoposide (ETO), are widely used in leukaemia. A patient with leukaemia has a relative infection with pneumonia treated by fluoroquinolones as moxifloxacin HCL (MOX). Because opioid analgesic as nalbuphine HCL (NAL) does not have a ceiling dose, it is used to manage the distasteful sensory in leukaemia. Consequently, green methods for synchronous spectrofluorimetric quantification of a ternary mixture of ETO, MOX and NAL were developed. The first approach relies simply on the estimation of MOX at 371 nm by conventional synchronous fluorimetric technique (Δλ of 60 nm). The second approach depends on applying the first derivative synchronous fluorimetric technique (Δλ of 60 nm) for simultaneous estimation of ETO and NAL at 257 and 273 nm, respectively. A good linear correlation was obtained in the ranges of 0.04-0.40, 0.10-1.00 and 0.50-5.00 µg ml-1 for MOX, ETO and NAL, respectively. Moreover, the proposed approaches were successfully applied for the estimation of the studied drugs in the pharmaceutical dosage forms. Additionally, the synchronous assessment of ETO, MOX and NAL in the spiked human urine was successfully attained by the facile protein precipitation technique. The mean % recoveries in spiked human urine were 99.49, 98.07 and 98.48 for MOX, ETO and NAL, respectively.

Epoxy and Polyester Composites' Characteristics under Tribological Loading Conditions.

This research examines the friction and dry wear behaviours of glass fibre-reinforced epoxy (GFRE) and glass fibre-reinforced polyester (GFRP) composites. Three fibre orientations-parallel orientation (P-O), anti-parallel orientation (AP-O), and normal orientation (N-O)-and various sliding distances from 0-15 km were examined. The experiments were carried out using a block-on-ring configuration at room temperature, an applied load of 30 N, and a sliding velocity of 2.8 m/s. During the sliding, interface temperatures and frictional forces were captured and recorded. Worn surfaces were examined using scanning electron microscopy to identify the damage. The highest wear rates for GFRE composites occurred in those with AP-O fibres, while the highest wear rates for GFRP composites occurred in those with P-O fibres. At longer sliding distances, composites with P-O and N-O fibres had the lowest wear rates. The highest friction coefficient was observed for composites with N-O and P-O fibres at higher sliding speeds. The lowest friction coefficient value (0.25) was for composites with AP-O fibres. GFRP composites with P-O fibres had a higher wear rate than those with N-O fibres at the maximum speed.

Pharmacokinetic interaction between atorvastatin and fixed-dose combination of sofosbuvir/ledipasvir in healthy male Egyptian volunteers.

PURPOSE: Comorbid conditions of heart and liver disorders added to HCV-induced hepatic steatosis make co-administration of statins, and direct-acting antivirals is common in clinical practice. This study aimed to evaluate the pharmacokinetic interaction of atorvastatin and fixed-dose combination of sofosbuvir/ledipasvir "FDCSL" with rationalization to the underlying mechanism. METHODS: A randomized, three-phase crossover study that involves 12 healthy volunteers was performed. Participants received a single-dose of atorvastatin 80 mg alone, atorvastatin 80-mg plus tablets containing 400/90 mg FDCSL, or tablets containing 400/90 mg FDCSL alone. Plasma samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for atorvastatin, sofosbuvir, ledipasvir, and sofosbuvir metabolite "GS-331007," and their pharmacokinetics parameters were determined. RESULTS: Compared to atorvastatin alone, the administration of FDCSL caused a significant increase in both areas under the concentration-time curve from time zero to infinity (AUC0-∞) and maximum plasma concentration (Cmax) of atorvastatin by 65.5% and 156.0%, respectively. Also, atorvastatin caused a significant increase in the AUC0-∞ and Cmax of sofosbuvir by 32.0% and 11.0%, respectively. Similarly, AUC0-∞ and Cmax of sofosbuvir metabolite significantly increased by 84.0% and 74.0%, respectively. However, ledipasvir AUC0-∞ showed no significant change after atorvastatin intake. The elimination rate in all drugs revealed no significant changes. CONCLUSION: After concurrent administration of FDCSL with atorvastatin, the AUC0-∞ of both atorvastatin and sofosbuvir were increased. Caution should be taken with close monitoring for possible side effects after co-administration of atorvastatin and FDCSL in clinical practice.

Multi-spectroscopic and molecular docking studies for binding interaction between fluvoxamine and human serum albumin.

In the present study, different spectroscopic techniques have been used to study the binding interaction between the antidepressant drug fluvoxamine and human serum albumin under simulated physiological conditions (pH 7.4). The utilized spectroscopic techniques include fluorescence emission spectroscopy, synchronous fluorescence spectroscopy, UV-Vis absorption spectroscopy, Fourier Transform Infrared spectroscopy (FT-IR), and molecular modeling methods. The obtained results revealed that the formation of a complex between human serum albumin and fluvoxamine was responsible for quenching the native fluorescence of human serum albumin. The results indicated that the quenching mechanism between human serum albumin and fluvoxamine was static. Besides, the binding constant (K), number of binding sites (n), thermodynamic parameters (ΔH, ΔS, and ΔG), and binding forces were calculated at three different temperatures (298, 310, and 318 K). These data proposed that hydrophobic forces were the principal intermolecular forces stabilizing the complex. From the molecular docking results, it could be deduced that fluvoxamine was inserted into sub-domain II A (site I) of human serum albumin and led to a slight change in human serum albumin conformation.

First derivative synchronous spectrofluorimetric method for the simultaneous determination of propofol and cisatracurium besylate in biological fluids.

Propofol and cisatracurium besylate have been simultaneously determined using a highly sensitive first derivative synchronous spectrofluorometric method. The method is based on measuring first derivative synchronous spectrofluorimetric amplitude at Δλ = 40 nm with a scanning rate of 600 nm/min. The different experimental parameters affecting the fluorescence intensity of the two drugs were carefully studied and optimized. The amplitude-concentration plots were rectilinear over the range 40.0-400.0 ng/mL and 20.0-280.0 ng/mL for propofol and cisatracurium, respectively with lower detection limits of 4.0 and 2.35 ng/mL and quantification limits of 12.1 and 7.1 ng/mL for propofol and cisatracurium, respectively. The proposed method was successfully applied for the determination of the two compounds in synthetic mixtures and in commercial ampoules. The high sensitivity attained using the proposed method allowed the simultaneous determination of both drugs in spiked plasma samples. The mean % recoveries in spiked human plasma (n = 3) were 96.53 ± 0.90 and 96.20 ± 1.64 for each of propofol and cisatracurium, respectively. The method was validated in compliance with International Council of Harmonization (ICH) Guidelines.

Conventional and first derivative synchronous spectrofluorimetric methods for the simultaneous determination of cisatracurium and nalbuphine in biological fluids.

Cisatracurium besylate has been determined by fast and highly sensitive spectrofluorimetric method based on measuring the fluorescence intensity of its methanolic solution at 312 nm after excitation at 230 nm (Method I). The linearity occurred over the concentration range of 10.0-130.0 ng/mL with detection limit of 1.07 ng/mL. The method was further extended for the determination of the studied drug in spiked human plasma with good percentage recoveries (97.43-103.50%). Cisatracurium is co-administered with nalbuphine during surgery. The simultaneous determination of both drugs was based on synchronous spectrofluorimetric technique. First derivative synchronous spectrofluorimetric amplitude was measured in methanol at Δ λ = 60 nm and each drug could be estimated at the zero crossing point of the other. Hence, cisatracurium could be measured at 284.6 nm while nalbuphine at 276.3 nm (Method II). The method was linear over the ranges of 50.0-750.0 ng/mL and 0.5-7.0 µg/mL with the detection limits of 2.16 ng/mL and 0.04 µg/mL for cisatracurium and nalbuphine, respectively. The method was further extended for the simultaneous determination of both drugs in spiked human urine with mean percentage recoveries of 99.99 ± 2.06 and 99.53 ± 6.17 for cisatracurium and nalbuphine, respectively. Both methods were validated in agreement with Guidelines adopted by International Council of Harmonization (ICH).

Simultaneous HPLC determination of alfuzosin, tamsulosin and vardenafil in human plasma and pharmaceutical formulations using time programmed fluorescence detection.

Alfuzosin and tamsulosin are recently co-administrated with vardenafil to treat symptoms of benign prostatic hyperplasia and erectile dysfunction. A highly sensitive and simple liquid chromatographic method was developed and validated for the simultaneous determination of the three drugs using moxifloxacin as an internal standard. Isocratic separation was achieved within 7.0 min using phenyl-hexyl column (250 × 4.6 mm i.d.) and a mobile phase composed of acetonitrile/0.25% phosphoric acid (30:70, v/v) at pH 3.0. The analysis was performed at a flow rate of 1.2 mL/min with fluorescence detection at 246/450 nm for Alfuzosin and vardenafil, and 226/322nm for tamsulosin using time programming technique. The proposed method was linear over the concentration ranges of 5.0-50.0ng/mL, 10.0-200.0ng/mL and 20.0-400.0ng/mL for alfuzosin, vardenafil and tamsulosin, with limits of detection of 0.56ng/mL, 0.98ng/mL and 2.81 ng/mL in a respective order. The developed method was successfully applied to determine the studied drugs in dosage forms and human plasma samples and the results were satisfactory as revealed by statistical analysis of the data.

Micellar HPLC-UV method for the simultaneous determination of levodopa, carbidopa and entacapone in pharmaceuticals and human plasma.

A method based on micellar liquid chromatography to quantify levodopa, carbidopa and entacapone in plasma is reported. The sample pretreatment was a simple dilution in a pure micellar solution then filtration and direct injection, without requiring extraction or purification steps. The three drugs were resolved from the matrix in 7 min, using an aqueous solution of 0.1 M sodium dodecyl sulphate-10% n-propanol-0.3 tiethylamine, adjusted at pH 2.8 with 0.02 M orthophosphoric acid as mobile phase, running under isocratic mode at 1.0 mL/ min through VP-ODS column. The detection was done by UV (ultraviolet) absorbance at 225 nm. The method was successfully validated by the International Conference Harmonization guidelines in terms of: selectivity, linearity (r2 > 0.998) over the concentration ranges of 0.025-1.2, 0.05-1.0 and 0.3-2.0 µg mL-1 with limits of detection of 0.01, 6.16 × 10-3 and 0.02 µg mL-1 and limits of quantification of 0.03, 0.02 and 0.07 µg mL-1 for levodopa, carbidopa and entacapone, respectively. The proposed method was applied successfully for quantification of the studied drugs in their different dosage forms. Moreover, the method was further extensive to the quantification of the studied drugs in spiked human plasma and was successfully validated by the guidelines of the European Medicines Agency. The proposed procedures were successfully evaluated to determine the studied drugs in real human plasma. The procedure was found reliable, practical, cost-effective, available, short period, easy-to-handle, low-cost, environmental-friendly, secure, useful for the analysis of numerous samples per day. Lastly, the method was performed to the analysis of incurred, using quality control samples in the same analytical run, with adequate results. Therefore, it can be implementable for custom analysis in clinical laboratories.

Simultaneous HPLC Determination of Cisatracurium and Propofol in Human Plasma via Fluorometric Detection.

The proposed method describes a high performance liquid chromatographic method with fluoremetric detection for the determination of cisatracurium (CIS) and propofol (PRP) simultaneously, which are co-administered as a pre-operative injection mixture. The separation of the two drugs was achieved using monolithic column (100 mm and 4.6 mm internal diameter) and mixture of methanol and 0.1 M phosphate buffer in the ratio of 80:20 (v/v) at pH 4.5 as a mobile phase. The fluorescence detection was carried out at 230/324 nm. The procedure showed good linearity through the concentration ranges of 0.01-1.00 µg/mL and 0.1-3.0 µg/mL with limits of detection of 0.002, 0.030 µg/mL and limits of quantification of 0.006, 0.100 µg/mL for CIS and PRP, respectively. Simultaneous determination of CIS and PRP in spiked human plasma samples was additionally executed and the results were satisfactory precise and accurate.

New spectrophotometric/chemometric assisted methods for the simultaneous determination of imatinib, gemifloxacin, nalbuphine and naproxen in pharmaceutical formulations and human urine.

In this paper, novel univariate and multivariate regression methods along with model-updating technique were developed and validated for the simultaneous determination of quaternary mixture of imatinib (IMB), gemifloxacin (GMI), nalbuphine (NLP) and naproxen (NAP). The univariate method is extended derivative ratio (EDR) which depends on measuring every drug in the quaternary mixture by using a ternary mixture of the other three drugs as divisor. Peak amplitudes were measured at 294nm, 250nm, 283nm and 239nm within linear concentration ranges of 4.0-17.0, 3.0-15.0, 4.0-80.0 and 1.0-6.0µgmL-1 for IMB, GMI, NLP and NAB, respectively. Multivariate methods adopted are partial least squares (PLS) in original and derivative mode. These models were constructed for simultaneous determination of the studied drugs in the ranges of 4.0-8.0, 3.0-11.0, 10.0-18.0 and 1.0-3.0µgmL-1 for IMB, GMI, NLP and NAB, respectively, by using eighteen mixtures as a calibration set and seven mixtures as a validation set. The root mean square error of predication (RMSEP) were 0.09 and 0.06 for IMB, 0.14 and 0.13 for GMI, 0.07 and 0.02 for NLP and 0.64 and 0.27 for NAP by PLS in original and derivative mode, respectively. Both models were successfully applied for analysis of IMB, GMI, NLP and NAP in their dosage forms. Updated PLS in derivative mode and EDR were applied for determination of the studied drugs in spiked human urine. The obtained results were statistically compared with those obtained by the reported methods giving a conclusion that there is no significant difference regarding accuracy and precision.

Micellar HPLC method for the simultaneous determination of three anticonvulsant drugs in dosage forms and biological fluids. Application to dissolution-rate testing.

This work describes a micellar liquid chromatographic method which was developed and validated to determine simultaneously three structurally-related antiepileptic drugs; namely carbamazepine (CMZ), oxcarbazepine (OCZ) and eslicarbazepine acetate (ECZ). The analysis was achieved using a phenyl column (250mm×4.6mm i.d., 5µm particle size), a mobile phase consisting of a mixture of 0.3% triethylamine and 10% n-butanol in a solution of 0.05M sodium dodecyl sulphate adjusted to pH 7.0 using 0.02M orthophosphoric acid. The mobile phase was pumped at a flow rate of 1.5mLmin-1 and detection was adjusted at 215nm. The method showed good linearity (r2>0.998) over the concentration ranges of 0.1-10 for CMZ and OCZ and 0.2-20µgmL-1 for ECZ. The suggested method was successfully applied for the analysis of the studied drugs in their dosage forms and for the determination of CMZ and OCZ in spiked human urine and plasma without prior extraction. The proposed method was further extended to the analysis of real samples of plasma and urine of volunteers receiving therapy of CMZ and OCZ. Furthermore, the method was successfully applied to tablets dissolution-rate testing, and the results were satisfactory.

Novel univariate and multivariate regression methods for the simultaneous analysis of ternary mixture of 1, 4-benzodiazepines in dosage forms and human urine.

In this paper, novel univariate and multivariate regression model updating methods were developed and validated for the simultaneous determination of ternary mixture of bromazepam, diazepam and clonazepam. The univariate methods used are the mean centering of ratio spectrophotometric method and iso-absorptive point coupled with ratio-subtraction and ratio difference spectrophotometric method. Linearity, ranges, precision and accuracy of these methods were determined. The multivariate methods adopted are the principal component regression and partial least-squares. These models were estimated using nineteen mixtures as calibration set and six mixtures as validation set. The minimum root square error of predication were 0.1215 and 0.0568 for BMZ, 0.0598 and 0.0712 for DIZ and 0.0867 and 0.0753 for CNP by PLS and PCR respectively. PCR and PLS methods were successfully applied for the analysis of BMZ, DIZ and CNP in their dosage forms. Content uniformity testing of the studied pharmaceutical tablets by PLS and PCR was also determined. MCR, IPRSRD and PLS model updating enabled the determination of BMZ, DIZ and CNP in spiked human urine. Moreover, PLS model updating was applied to drug-dissolution rate testing of BMZ and DIZ in their commercial tablets. The obtained results were statistically compared with those obtained by reported methods giving a conclusion that there is no significant difference regarding accuracy and precision.

Micelle-enhanced spectrofluorimetric method for quantification of entacapone in tablets and human plasma.

In this paper, a simple and highly sensitive spectrofluorimetric method was developed and validated for the determination of entacapone (ETC). The proposed method is based on forming a highly fluorescent product through the reduction of ETC with Zn/HCl. The produced fluorophore exhibits strong fluorescence at λem 345 nm after excitation at λex 240 nm. The use of fluorescence enhancers such as Tween-80 and carboxy methyl cellulose (CMC) greatly enhanced the fluorescence of the produced fluorophore by 150% and 200%, respectively. Calibration curves showed good linear regression (r2 > 0.9998) within test ranges of 0.05-2.0 and 0.02-1.80 µg mL-1 with lower detection limits of 1.27 × 10-2 and 4.8 × 10-3  µg mL-1 and lower quantification limits of 4.21 × 10-2 and 1.61 × 10-2  µg mL-1 upon using Tween-80 and or CMC, respectively. The method was successfully applied to the analysis of ETC in its pharmaceutical formulations (either alone or in presence of other co-formulated drugs). The results were in good agreement with those obtained using the official method. The methods were further extended to determine the drug in human plasma samples, and to study the pharmacokinetics of ETC. The paper is the first report on the spectrofluorimetric determination of entacapone.