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A
A.Merey, H., F. A.Morsy, M. A.Mohammed, and M. Y.Salem, "Determination of oxybuprocaine HCL in pharmaceutical formulations using thermal techniques", Analytical Chemistry An Indian Journal , vol. 15, issue 9, pp. 379-386, 2015. Abstract

The thermal behavior of oxybuprocaine hydrochloride (OXY) has been studied.
Thermogravimetric analysis (TGA), derivative thermogravimetry (DTG)
and differential thermal analysis (DTA) techniques were used to study the
thermal behavior of the drug.
Thermal-analytical study showed that OXY is thermally decomposed in
four steps. The first step occurs in the temperature range of 62.05- 166.70 ºC,
the second step occurs at 166.70 -354.91 ºC, the third step occurs at 354.91
- 455.52 ºC and the fourth step at 455.52–489.05 ºC. Melting point of OXP
was recorded at 160.15 ºC.
Thermodynamic parameters such as activation energy (Ea), frequency factor
(A), reaction order (n), and correlation coefficient (r) were calculated
using different kinetic models. The purity value for the drug was found to
be 99.36%. Thermal analysis technique gave satisfactory results to obtain
quality control parameters such as melting point, water content and ash
content in comparison to those obtained using official methods. Thermal
analysis justifies its application in quality control of pharmaceutical compounds
due to its simplicity, sensitivity and low operational costs. DSC
results indicated that the degree of purity of Oxybuprocaine HCl is similar
to that found by official method.

A.Merey, H., M. S. Abd-Elmonem, H. N. Nazlawy, and H. E. Zaazaa, "Spectrophotometric Methods for Simultaneous Determination of Oxytetracycline HCl and Flunixin Meglumine in Their Veterinary Pharmaceutical Formulation", Journal of Analytical Methods in Chemistry, vol. https://doi.org/10.1155/2017/2321572, 2017.
Alamein, A. A. A. M., H. A. Merey, R. E. A. Kalla, and A. E. E. Gendy, "Validated Spectrophotometric Methods for Simultaneous Determination of Sulphadoxine and trimethoprim in a Veterinary Pharmaceutical Dosage Form", Research J. Pharm. and Tech. , vol. 13, issue 11, pp. 5151-5157, 2020.
E
Elmasry, M. S., W. S. Hassan, H. A. Merey, and I. M. Nour, "Simple mathematical data processing method for the determination of sever overlapped spectra of linagliptin and empagliflozin in their pure forms and pharmaceutical formulation: Fourier self deconvulated method.", Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, vol. 254, pp. 119609, 2021. Abstract

A new and simple spectrophotometric method was developed for the simultaneous determination of a new antidiabetic mixture of linagliptin and empagliflozin namely fourier self deconvulated method. The developed method based on minimal mathematical data processing on the zero order spectrum for solving sever overlapping spectra of the mentioned drugs in their pure forms and pharmaceutical dosage form. The zero order spectra of linagliptin and empagliflozin were deconvulated using Fourier transforms function. The peak amplitudes at 232 nm were selected for linagliptin and at 239 nm for empagliflozin. The constructed calibration graphs were linear over the range (5-30 µg/mL) and (2-12 µg/mL) for empagliflozin and linagliptin, respectively. The adopted method was simple, accurate, precise and validated according to the ICH guidelines.

Elmasry, M. S., M. A. Hasan, W. S. Hassan, H. A. Merey, and I. M. Nour, "Flourimetric study on antidiabetic combined drugs; empagliflozin and linagliptin in their pharmaceutical formulation and human plasma.", Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, vol. 248, pp. 119258, 2021. Abstract

Empagliflozin and linagliptin are newly approved FDA combination that used for the treatment of type 2 diabetes mellitus (T2DM) under trade name Glxambi. Two spectroflourimetric methods were developed for simple quantitative determination of empagliflozin and linagliptin in their pharmaceutical formulation and human plasma without need any tedious processing operations. Empagliflozin has a native fluorescence nature, therefore can be directly determined by measuring emission peak at 305 nm after excitation at 234 nm. There is no any interference from linagliptin at this emission wavelength. On the other hand, linagliptin is a very weak florescent compound that needs to react with fluorogenic reagent to be quantitatively determined without any reaction of empagliflozin. So, quantitative analysis of linagliptin was achieved by coupling with NBD-Cl which is an electro active halide reagent (targeting only Linagliptin with no effect on empagliflozin). Dark yellow fluorophore with high fluorescence is a result of this reaction and can be measured at emission wavelength 538 nm after excition at wavelength 469 nm. Experimental conditions of the suggested methods were well checked and optimized. The regression plots were found to be linear over the range of 40-1200 ng/mL and 3-700 ng/mL for empagliflozin and linagliptin, respectively. The obtained results by the suggested methods were statistically compared with those obtained by the reported methods, showing no significant difference with respect to accuracy and precision at p = 0.05.

Elzanfaly, E. S., and H. A. Merey, "A Liquid Chromatography/Tandem Mass Spectrometric Method for Determination of Captopril in Human Plasma: Application to a Bioequivalence Study", Journal of Applied Pharmaceutical Science, vol. 7, issue 2, pp. 8-15, 2017. Abstract

A simple, rapid and sensitive ultra-performance liquid chromatography/positive ion electrospray tandem mass

spectrometric method was developed and validated for the quantification of captopril in human plasma.

Following plasma protein precipitation, the analyte and internal standard Rosuvastatin were separated by ultra-
performance liquid chromatography using a gradient mode mobile phase on a reversed-phase column and

analyzed by mass spectrometry in the multiple reaction monitoring mode (MRM) using the respective [MRH]R

ions, m/z 218.09/116.16 for captopril and m/z 482.2/ 258.17 for the internal standard. The method exhibited a

linear dynamic range of 10–2000 ng/mL for captopril in human plasma. The lower limit of quantification

was 10 ng/mL with a relative standard deviation of less than 6%. Acceptable precision and accuracy were

obtained for concentrations over the standard curve range. A total run time of 3 minutes for each sample made it

possible to analyze more than 20 human plasma samples per one hour. The validated method has been

successfully applied to analyze human plasma samples in a bioequivalence study of captopril after oral

administration of 50 mg captopril tablet to 24 healthy subjects.

Elzanfaly, E. S., H. E. Zaazaa, and H. A. Merey, "Ion selective phosphotungestate and β-cyclodextrin based membrane electrodes for stability-indicating determination of midodrine hydrochloride", Acta Chimica Slovenica, vol. 60, issue (2), pp. 256-262, 2013. Abstract

This paper reports the construction and evaluation of two ion selective electrodes for the determination midodrine hydrochloride (MD) by direct potentiometry in pure drug substance and in tablet formulations. Precipitation based technique was used for fabrication of the first membrane sensor (sensor 1) using phosphotungestate (PT) and dioctylphthalate (DOP), as cation exchanger and solvent mediator, respectively. β-cyclodextrin (β-CD)-based technique with PT as a fixed anionic site in PVC matrix was used for fabrication of the second membrane sensor (sensor 2). The proposed sensors showed fast, stable Nernstian responses of 54 and 57 mV/decade for sensors 1 and 2, respectively, across a relatively wide MD concentration range (1x10-4 to 1x10-1 mol/L and 5x10-5 to 1x10-1 mol/L) for sensor 1 and 2, respectively , in the pH range of 4.5-7.5. Sensor 1 and sensor 2 can be used for three and two weeks, respectively without any measurable change in sensitivity. The suggested electrodes succeeded to determine intact (MD) in the presence of up to 10% of its degradate and displayed good selectivity in presence of common inorganic and organic species.

H
H. A. Merey, S. S. El-Mosallamy, N. Y. Hassan, and B. A. El-Zeany, "Validated eco--friendly spectrophotometric methods for the determination of acefylline piperazine and bromhexine hydrochloride in the presence of dosage form additives", Journal of Applied Spectroscopy, vol. 87, issue 1, pp. 159-168, 2020.
H. A. Merey, S. S. El-Mosallamy, N. Y. Hassan, and B. A. El-Zeany, "Green monitoring of bromhexine oxidative degradation kinetics", Microchemical Journal, vol. 152, pp. 104378, 2020. Abstract

Kinetics studies are important in quality control to assure the safety and efficacy of the pharmaceutical compounds.
Recently, potentiometric ion-selective electrodes (ISEs) breakthrough kinetics study due to their ability
to provide real-time measurements which meet “green analytical chemistry” (GAC) principles. A polyvinyl
chloride (PVC) matrix membrane was fabricated to monitor bromhexine (BR) oxidative degradation kinetics
using tetraphenylborate as a cation exchanger. At-line monitoring of the oxidative degradation kinetics of BR was
performed; by continuous measuring the decrease in the sensor potential over time. So a real-time observation
and a continuous profile were obtained for the oxidation of BR under various H2O2 concentrations and temperature.
This kinetic study determines the oxidation activation energy that was 6.4 kcal mol−1. To expand the
application of this sensor, BR was determined in bulk powder and dosage form in the presence of both coformulated
drug (acefylline piperazine) and dosage form additives. The proposed sensor had been characterized
according to IUPAC recommendations and a linear dynamic range was 5×10−6 to 1×10−3M and other sensor
parameters had been calculated.

H. A. Merey, N. K.Ramadan, S. S. Diab, and A. A. Moustafa, "Green spectrophotometric methods for the determination of a binary mixture of lidocaine hydrochloride and cetylpyridinium chloride in the presence of dimethylaniline", Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 242 , pp. 118743, 2020. Abstract

Three green, simple, precise, accurate and sensitive spectrophotometric methods were developed for the determination
of a binary mixture of lidocaine hydrochloride (LDC) and cetylpyridinium chloride (CPC) in the presence
of dimethylaniline (DMA). In the three methods, the interference of DMA spectrum is eliminated using
the ratio subtraction method. Method (A) depended on determining LDC and CPC by measuring the first derivative
of the ratio spectra (1DD) at 271.0 and 268.4 nm, respectively. Method (B) was the ratio difference (RD),
based on dividing the absorption spectrum of the binary mixture by a standard spectrum of CPC or LDC, then
measuring the amplitude difference of the ratio spectra (ΔP) between 231.2 and 240.0 nm for LDC and between
242.8 and 258.0 nm for CPC. Method (C) based on the application of dual wavelength coupled with the
isoabsorptive point method. This was achieved by measuring the absorbance difference (ΔA) between 243.0
and 268.6 nm for the determination of LDC, followed by application of isoabsorptive point method comprised
ofmeasurement the total content of the mixture of LDC and CPC at their isoabsorptive point at 240.0nm. The content
of CPCwas obtained by subtraction. The specificity of the developed methods was investigated by analyzing
laboratory prepared mixtures containing different ratios of LDC and CPC in presence of DMA. The proposed
methods displayed useful analytical characteristics for the determination of LDC and CPC in bulk powder and
their combined dosage form. The obtained results were statistically comparedwith those obtained by the official
methods, showing no significant difference with respect to accuracy and precision.

I
Ibrahim, H., A. M. Hamdy, H. A. Merey, and A. S. Saad, "Dual-Mode Gradient HPLC and TLC Densitometry Methods for the Simultaneous Determination of Paracetamol and Methionine in the Presence of Paracetamol Impurities.", Journal of AOAC International, vol. 104, issue 4, pp. 975-982, 2021. Abstract

BACKGROUND: Paracetamol (PC) is one of the most widely used analgesic and antipyretic drugs and has recently been integrated into the supportive therapy of COVID-19. Pharmaceuticals containing methionine (MT) with PC may contribute to avoid hepatotoxicity and eventual PC overdose-dependent death.

OBJECTIVE: The current work purposes to develop and validate two chromatographic methods for the simultaneous determination of MT and PC in the presence of two PC impurities (4-nitrophenol [NP] and 4-aminophenol [AP]).

METHOD: Two chromatographic methods were established and validated according to the International Conference on Harmonization guidelines. The first one was an RP-HPLC/UV method based on applying a "dual-mode" gradient elution. The separation was realized via varying both the composition of the ternary mobile phase (acetonitrile-methanol-water) and its flow rate. This strategy enabled a relatively rapid analysis with a satisfactory resolution, although the investigated compounds exhibit a significant difference in lipophilicity. The second one relied on TLC-densitometry, where the optimum separation was realized using a quaternary mobile phase system composed of butanol-dioxane-toluene-methanol (8:2.5:3.5:0.3, by volume). Both methods were monitored at 220 nm.

RESULTS: The developed methods were proven to be robust, accurate, specific, and appropriate for the routine analysis of PC in its pure form or in pharmaceutical formulations with MT in quality control laboratories.

CONCLUSIONS: The corresponding methods are suitable to determine MT and PC in the presence of PC impurities.

HIGHLIGHTS: The study achieves the analysis of MT and PC in the presence of PC impurities via the application of HPLC and TLC-densitometry methods.

Ibrahim, H., A. M. Hamdy, H. A. Merey, and A. S. Saad, "Simultaneous Determination of Paracetamol, Propyphenazone and Caffeine in Presence of Paracetamol Impurities Using Dual-Mode Gradient HPLC and TLC Densitometry Methods.", Journal of chromatographic science, vol. 59, issue 2, pp. 140-147, 2021. Abstract

Two chromatographic methods were validated for the determination of the widely prescribed analgesic and antipyretic drug combination of paracetamol (PC) (recently integrated into the supportive treatment of COVID-19), propyphenazone (PZ) and caffeine (CF) in the presence of two PC impurities, namely 4-aminophenol and 4-nitrophenol. A "dual-mode" gradient high-performance liquid chromatography method was developed, where the separation was achieved via "dual-mode" gradient by changing both the ternary mobile phase composition (acetonitrile: methanol: water) and the flow rate. This enables a good resolution within a relatively shorter analysis time. The analysis was realized using Zorbax Eclipse XDB column C18, 5 μm (250 × 4.6 mm) and the UV detector was set at 220 nm. The other method is a thin-layer chromatography densitometry method, where the separation was achieved using a mobile phase composed of chloroform: toluene: ethyl acetate: methanol: acetic acid (6: 6: 1: 2: 0.1, by volume). Densitometric detection was performed at 220 nm on silica gel 60 F254 plates. The developed methods were fully validated as per the ICH guidelines and proved to be accurate, robust, specific and suitable for application as purity indicating methods for routine analysis of PC in pure form or in pharmaceuticals with PZ and CF in quality control laboratories.

K
K.Ramadan, N., H. E. Zaazaa, and H. A. Merey, "Micronized graphite sensors for potentiometric determination of cyclobenzaprine hydrochloride", Journal of AOAC International, vol. 94, issue 6, pp. 1807-1814, 2011. Abstract

Two cyclobenzaprine hydrochloride (CZ) microsized graphite selective sensors were investigated with dibutylsebacate as a plasticizer in a polymeric matrix of carboxylated polyvinyl chloride (PVC-COOH) in the case of sensor 1, based on the interaction between the drug and the dissociated COOH groups in the PVC-COOH. Sensor 2 was based on the interaction between the drug and ammonium reineckate, which acted as anionic electroactive material in the presence of polyvinyl chloride matrix. The two sensors were constructed by using 2-hydroxy propyl β-cyclodextrin as an ionophore, which has a significant influence on increasing the membrane sensitivity and selectivity of both sensors. Fast and stable Nernstian responses of 1 × 10–5–1 × 10–2 and 1 × 10–4–1 × 10–2 M for the two sensors, respectively, with slopes of 58.6 and 55.5 mV/decade, respectively, over the pH range 2–4 were obtained. The proposed method displayed useful analytical characteristics for determination of CZ in its pure powder form with average recoveries 99.95 ± 0.23 and 99.61 ± 0.34% for sensors 1 and 2, respectively, and in plasma with good recoveries. The sensors were also used to determine the intact drug in the presence of its degradate and, thus, could be used as stability-indicating methods. The obtained results by the proposed methods were statistically analyzed and compared with those obtained by the U.S. Pharmacopeia method; no significant difference for either accuracy or precision was observed. Results obtained with the two electrodes revealed their performance characteristics, which were evaluated according to International Union of Pure and Applied Chemistry recommendations.

M
Merey, H. A., S. S. El-Mosallamy, N. Y. Hassan, and B. A. El-Zeany, "Simultaneous determination of Fluticasone propionate and Azelastine hydrochloride in the presence of pharmaceutical dosage form additives", Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 160, pp. 50-57, 2016. Abstract

Fluticasone propionate (FLU) and Azelastine hydrochloride (AZE) are co-formulated with phenylethyl alcohol
(PEA) and Benzalkonium chloride (BENZ) (as preservatives) in pharmaceutical dosage form for treatment of seasonal
allergies. Different spectrophotometric methods were used for the simultaneous determination of cited
drugs in the dosage form. Direct spectrophotometric method was used for determining of AZE, while Derivative
of double divisor of ratio spectra (DD-RS), Ratio subtraction coupled with ratio difference method (RS-RD) and
Mean centering of the ratio spectra (MCR) are used for the determination of FLU. The linearity of the proposed
methods was investigated in the range of 5.00–40.00 and 5.00–80.00 μg/mL for FLU and AZE, respectively. The
specificity of the developed methods was investigated by analyzing laboratory prepared mixtures containing different
ratios of cited drugs in addition to PEA and their pharmaceutical dosage form. The validity of the proposed
methods was assessed using the standard addition technique. The obtained results were statistically compared
with those obtained by official or the reported method for FLU or AZE, respectively showing no significant difference
with respect to accuracy and precision at p = 0.05.

Merey, H. A., M. M. Galal, M. Y. Salem, and E. M. Abdel-Moety, "Chromatographic determination of tamoxifen citrate in presence of some co-administered drugs", Journal of Pharmacy Research, vol. 8, issue 4, pp. 2458-2461, 2011. Abstract

Tamoxifen citrate (TC) is a selective estrogen receptor modifier (SERM) that is usually used in the treatment of breast cancer which is associated with high levels of cyclooxygenase enzyme. Some new non-steroidal anti-inflammatory drugs (NSAIDs) are effective in preventing estrogen receptor-positive tumors, which currently can be prevented and treated with drugs such as tamoxifen citrate. In this work, a high performance liquid chromatographic method is described for the determination of the (TC) in the presence of some usually prescribed NSAIDs, namely, ibuprofen or paracetamol. The analysis is carried out on Zorbax ODS C18 column using mobile phase consisting of methanol: 1 % triethylamine (89: 11, by volumes) at pH = 4 (adjusted using o-phosphoric acid) and flow rate of 1 ml/min.
The method has been validated according to USP guidelines and the system suitability parameters have been calculated. The method is successfully applied for the determination of the drugs in pure powdered forms, pharmaceutical dosage formulations and in spiked plasma samples.

Merey, H. A., M. I. Helmy, S. M. Tawakkol, S. S. Toubar, and M. S. Risk, "Potentiometric membrane sensors for determination of memantine hydrochloride and promipexole dihydrochloride monohydrate", Portugaliae Electrochimica Acta, vol. 30, issue 1, pp. 31-43, 2012. Abstract

Five solid membrane sensors responsive to memantine hydrochloride (MEM) and pramipexole dihydrochloride monohydrate (PXL) are described for simple and fast determination of these drugs in pharmaceutical preparation and human plasma. The first and the second sensors are based on the formation of an ion association complex between MEM as a cationic drug with Na tetra phenyl borate and ammonium reineckate (as anionic exchanger), respectively. The third sensor is based on the formation of an ion association complex between PXL with ammonium reineckate. The produced electroactive material is dispersed in PVC matrix. While the other fourth and fifth sensors are based on using functionalized lipophilic cyclodextrin derivative (2-hydroxypropyl-β-cyclodextrin) as sensor ionophore for the determination of MEM and PXL. The performance characteristics of these sensors - evaluated according to IUPAC recommendations - reveal fast, stable and near Nernstian response for 1x10-4-1x10-1 M and 1x10-6-1x10-2 M for (MEM) and (PXL), respectively. Many inorganic and organic substances such as drug excipients and diluents normally used in drug formulations do not interfere with drugs response. Statistical comparison between the results obtained by applying the proposed potentiometric method for the determination of the (MEM) and (PXL) in their pure powder forms and those obtained by applying the reported methods was done and no significant difference was found at p=0.05. Validation of the method according to ICH guidelines shows the suitability of the sensors for quality control analysis of the cited drugs in pharmaceutical formulations and human plasma. The proposed sensors can also be used as a detector for HPLC.

Merey, H. A., N. K. Ramadan, S. S. Diab, and A. A. Moustafa, "Spectrophotometric methods for simultaneous determination of ternary mixture of amlodipine besylate, olmesartan medoxomil and hydrochlorothiazide", Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 125, pp. 138-146, 2014.
Merey, H. A., N. K. Ramadan, S. S. Diab, and A. A. Moustafa, "Chromatographic methods for the simultaneous determination of binary mixture of Saxagliptin HCl and Metformin HCl", Bulletin of Faculty of Pharmacy, Cairo University, vol. 55 , pp. 311-317, 2017. paper.pdf
Merey, H. A., F. A. Morsy, M. A. Mohammed, and M. Y. Salem, "Development and validation of novel stability indicating methods for estimation of amylocaine hydrochloride in bulk and dosage form ", Analytical Chemistry An Indian Journal, vol. 12, issue 3, pp. 103-110, 2013. Abstract

Three sensitive and selective methods were developed and validated as stability indicating methods for the determination of amylocaine HCl in presence of its degradation product. The second method is a spectro-densitometric method for the determination of amylocaine HCl after separation from its degradation product and additives of pharmaceutical dosage form using toluene: methanol: chloroform: 10%NH3 (5:3:6:0.1 v/v) followed by detection at 234 nm. The third method is an isocratic high performance liquid chromatographicmethod (HPLC) on a reversed phase C18 column using mobile phase consisting of distilled water: acetonitrile: triethylamine (530: 470: 0.1v/v) and the pH was adjusted to 3 by o-phosphoric acid. The proposed methods were successfully applied for the analysis of amylocaine HCl in laboratory prepared mixtures and in pharmaceutical dosage form and the results obtained were assessed by applying the standard addition technique. Statistical comparison between the results obtained by applying the proposed methods and manufacturer's method for amylocaine HCl in its pure powder form was done and no significant difference was found at p = 0.05.

Merey, H. A., "Simple spectrophotometric methods for the simultaneous determination of antipyrine and benzocaine", Bulletin of Faculty of Pharmacy, Cairo University, vol. 54, pp. 181-189, 2016. Abstract

Antipyrine and benzocaine are formulated together for the treatment of ear inflammation
and to relieve pain. Four spectrophotometric methods were developed for the simultaneous
determination of antipyrine (AN) and benzocaine (BE) in their combined dosage form. Method
A depends on applying dual wavelength method where antipyrine was determined by measuring
the absorbance at 254.1 and 309.1 nm (corresponding to zero difference of benzocaine), while the
absorbance difference at 230.1 and 263.5 nm (corresponding to zero difference of antipyrine) was
selected for benzocaine determination in the laboratory prepared spectrum. Method B depends
on measuring the peak amplitude of first derivative at 305 nm for calculating benzocaine concentration
then the total concentration of both drugs was determined using isoabsorptive point at
257.4 nm (antipyrine concentration was then calculated by subtraction). Method C is based on measuring
the peak difference of the ratio spectra at Dp (239.1–285 nm) and Dp (301.4–250 nm) for the
determination of antipyrine and benzocaine, respectively. Method D depends on measuring peak to
peak amplitude of the first derivative of ratio spectra at (234.5 + 244.2 nm) and peak amplitude at
295.5 nm for the determination of antipyrine and benzocaine, respectively. The proposed methods
were validated and applied for the analysis of antipyrine and benzocaine in their laboratory prepared
mixtures and pharmaceutical formulation. Statistical comparison between the results of
the proposed methods and those of the reported methods showed no significant difference.

Merey, H. A., S. S. El-Mosallamy, N. Y. Hassan, and B. A. El-Zeany, "Validated chromatographic methods for the simultaneous determination of Mometasone furoate and Formoterol fumarate dihydrate in a combined dosage form", Bulletin of Faculty of Pharmacy, Cairo University, vol. 54, pp. 99-106, 2016. Abstract

Two chromatographic methods were developed and validated for the simultaneous
determination of Mometasone furoate (MO) and Formoterol fumarate dihydrate (FOR). Combination
of MO and FOR is used for the treatment of asthma in patients suffering from reversible
obstructive airway disease. The first chromatographic method was based on using aluminum
TLC plates pre-coated with silica gel GF254 as the stationary phase and chloroform:ethyl acetate:
methanol:toluene:formic acid (5:2:2:2:0.1, by volume) as the mobile phase followed by densitometric
measurement of the separated bands at 233 nm. The second method is a high performance liquid
chromatographic method for the separation and determination of MO and FOR using reversed
phase C18 column with isocratic elution. The mobile phase composed of methanol: 0.5% ammonium
acetate pH adjusted with acetic acid (80:20, v/v) at a flow rate of 1.0 mL/min. Quantitation
was achieved with UV detection at 220 nm. The specificity of the developed methods was investigated
by analyzing the pharmaceutical dosage form. The validity of the proposed methods was
assessed using the standard addition technique. The obtained results were statistically compared
with those obtained by the reported methods, showing no significant difference with respect to accuracy
and precision at p = 0.05.

Merey, H. A., and H. E. Zaazaa, "Validated simultaneous determination of antipyrine and benzocaine HCl in the presence of benzocaine HCl degradation product", Analytical Methods, vol. 6, pp. 6044–6050, 2014.
Merey, H. A., M. A. Mohammed, F. A. Morsy, and M. Y. Salem, "Simultaneous determination of pramocaine HCl and hydrocortisone acetate in pharmaceutical dosage form", Journal of Liquid Chromatography & Related Technologies, vol. 36, issue (19), pp. 2774-2784, 2013. Abstract

Two sensitive and selective methods were developed and validated for simultaneous determination of pramocaine HCl and hydrocortisone acetate in pharmaceutical dosage form. The first method is a spectro-densitometric method where pramocaine HCl and hydrocortisone acetate were separated using toluene: methanol: chloroform: 10% NH3 (5:3:6:0.1, by volume) as developing system followed by densitometric measurement at 290 nm. The second method is a high performance liquid chromatographic method for separation and determination of both drugs using reversed phase C18 column and mobile phase consisting of distilled water: acetonitrile: triethylamine (530: 470: 0.1, by volume), pH was adjusted to 3 by o-phosphoric acid. The proposed methods were successfully applied for the analysis of pramocaine HCl and hydrocortisone acetate in laboratory prepared mixtures and in pharmaceutical dosage form and the results obtained were assessed by applying the standard addition technique. Statistical comparison between the results obtained by applying the proposed methods and official method for the cited drugs was done and no significant difference was found at p = 0.05

Merey, H. A., S. S. El-Mosallamy, N. Y. Hassan, and B. A. El-Zeany, "Spectrophotometric and Chemometric Study for the Simultaneous Determination of Mometasone Furoate and Miconazole Nitrate in the presence of Pharmaceutical Dosage Form Additive", Analytical Chemistry Letters, vol. 6, issue 1, pp. 70-85, 2016. Abstract

Mometasone Furoate (MO) and Miconazole Nitrate (MI) are co-formulated with p-chlorometa-cresol
(CMC) which added in pharmaceutical dosage form as a preservative together for treatment of skin
infections by candida or dermatophyte in which inflammatory and pruritic manifestation are prominent.
Comparative study between different specrtophotometric methods were done for the simultaneous determination
of cited drugs in the dosage form. Spectrophotometric methods were used including, derivative ratio spectra
(DD), derivative of double divisor of ratio spectra (DD-RS) and Mean centering of the ratio spectra (MCR).
While the chemometric methods were used including, partial least-squares (PLS) and principal component
regression (PCR). The linearity of the proposed methods was investigated in the range of 3-33 and 60-840 μg/
mL for MO and MI, respectively. The specificity of the developed methods was investigated by analyzing
laboratory prepared mixtures containing different ratios of cited drugs in addition to CMC and their pharmaceutical
dosage form. The validity of the proposed methods was assessed using the standard addition technique. The
obtained results were statistically compared with those obtained by the reported method, showing no significant
difference with respect to accuracy and precision at p = 0.05.