Hanan Merey

Three new simple and selective assays were developed for the analysis of binary mixture
containing timolol maleate (TM) and brimonidine tartarate (BT) in the presence of benzalkonium chloride
(BZ) as a preservative in eye drops. The first derivative ultraviolet spectrophotometry was used with zerocrossing
measurements at 313 nm for TM and 386 nm for BT, respectively. The second method depends on the
first derivative of the ratio spectra with zero-crossing measurements at 313 nm and 391 nm for TM and BT,
respectively using 0.25 μg/mL BZ as a divisor. The assays were linear over the concentration ranges 5-85 μg/
mL and 2-35 μg/mL for TM and BT, respectively. The third method was based on isocratic and mobile phase
saving micellar liquid chromatographic method with a Biobasic phenyl column (150 x 1.0 mm, 5 μm particle
size) and micellar mobile phase composed of 0.1M SDS, 10 % of 1-propanol and 0.1 % of TEA in 0.035M
ortho phosphoric acid. UV detection was adjusted at 298 nm and 250 nm for TM and BT, respectively performed
at room temperature. The linearity range for TM and BT was 2-100 μg/mL and 1-50 μg/mL, respectively. The
proposed methods showed high percentage recovery, good accuracy and precision.

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.

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.

A potentiometricmembrane sensor responsive with satisfactory selectivity
to clindamycin hydrochloride was prepared for simple and fast
determination of this drug in pure form and pharmaceutical dosage forms
without prior extraction process or separation from different dosage form
excipients. The sensor was based on the formation of an ion association
complex between clindamycin hydrochloride as a cationic drug and sodium
phosphotungestate as anionic electroactive material. The produced ion
association complex was incorporated in plasticized polyvinyl chloride
membrane. The performance characteristics of this sensors were evaluated
according to IUPAC recommendations-reveal fast, stable and near
Nernestian response for 3.16 × 10-4 - 1 × 10-1 M for clindamycin
hydrochloride. Statistical comparison between the results obtained by
applying the proposed potentiometric method for the determination of the
clindamycin hydrochloride and those obtained by applying the official
method was done and no significant difference was found at p = 0.05.
Validation of themethod according to ICH guidelines shows the suitability
of the sensor for quality control analysis of the cited drugs in
pharmaceutical formulations. The proposed sensors can also be used as a
detector for HPLCmethod.

Tamoxifen citrate (TC) and raloxifene hydrochloride (RH) are two selective estrogen receptor modifiers. TC is usually used in the treatment of breast cancer while RH is used in the treatment of osteoporosis. Two stability indicating methods, namely, first derivative of ratio spectra (1DD) and TLC-densitometric method are used for the determination of TC in the presence of its photodegradants and RH in the presence of its oxidative degradants. For the first derivative of ratio spectra method, TC was quantitatively measured at 263 nm and 298.2 nm in a concentration range of 10–60 µg/mL while RH was determined at 267.6 nm in a concentration range of 2–18 µg/mL. In the spectro-densitometric method, TC was separated from its photodegradants using a developing system consisting of acetonitrile: 33% ammonia solution (10: 0.1, v/v) in a concentration range of 6–20 µg/band while RH was separated from its oxidative degradants using ethyl acetate: methanol: 33% ammonia solution (7: 3: 0.1, by volume) as a developing system in a concentration range of 3–11 µg/band.
The two methods were successfully applied for the stability indicating the determination of the two drugs in a pure powdered form and a pharmaceutical dosage form and showing good recoveries. Statistical comparison between the results obtained by applying the proposed methods and the official method or the reported method for TC and RH, respectively was done and no significant difference was found at p=0.05.

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

Four novel pramoxine HCl (PAM) selective electrodes were investigated with 2-nitrophenyl octylether as a plasticiser in a polymeric matrix of polyvinyl chloride (PVC). Sensor 1 was fabricated using sodium-tetraphenylborate (TPB) as an anionic exchanger without incorporation of an ionophore. Sensor 2 used 2-hydroxy propyl -cyclodextrin as an ionophore, while sensors 3 and 4 were constructed using 4-sulfocalix-6-arene and 4-sulfocalix-8-arene respectively as ionophores. Linear responses of PAM within the concentration ranges of 1.0x10−4 to 1.0x10−2 mol.L-1 and 1.0x10−5 to 1.0x10−2 mol.L-1 were obtained using sensors 1 and 2, respectively and 1.0x10−6 to 1.0x10−2 mol.L-1 were obtained using sensors 3 and 4. Nernstian slopes of 50.4±0.6, 54.3±0.8, 56.3±0.3 and 59.1±0.5 mV/decade over the pH range of 3.0–6.0 were observed. The selectivity coefficients of the developed sensors indicated excellent selectivity for PAM. The utility of 2-hydroxy- propylcyclodextrin (2HP-β-CD) and 4-sulfocalix [6, 8] arene (SC 6, 8) as ionophores had a significant influence on increasing the membrane sensitivity and selectivity of sensors 2, 3 and 4 compared to sensor 1. The proposed sensors displayed useful analytical characteristics for the determination of PAM in bulk powder, pharmaceutical formulation, and in biological fluid. Validation of the method showed the suitability of the proposed electrodes for the use in the quality control assessment of the drug. Furthermore, statistical comparison between the results obtained by the proposed method and the official method of the drug was performed and no significant difference was found.

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.

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.

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.

Two simple, accurate and precise methods are described for the determination of some non-steroidal estrogen level modifiers in pure powder form and pharmaceutical dosage forms. The first method is based on the reduction of ferric phenanthrolene (ferriin) to ferroin by Tamoxifen citrate (I) or Clomiphene citrate (II). The obtained ferroin chelate has an orange red color ( λmax 510.5 nm) measurable in concentration ranges of 2-9 µg/ml and 1-7 µg/ml for I and II, respectively. The second method is based on charge-transfer complexation between 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) as electron acceptor and (I) or Raloxifene hydrochloride (III) as the electron donors. The produced red color can be measured at λmax 458.5 nm in the concentration ranges of 40-280 µg/ml and 80-320 µg/ml for I & III, in orders. Different factors affecting the color formation have been studied and optimized and the proposed methods were successfully applied for the determination of the named drugs in their pharmaceutical formulations.