Synthesis of molecularly imprinted polymer for selective solid-phase extraction of Salbutamol from urine samples
- Mohammadi, Ali, Alizadeh, Taher, Dinarvand, Rassoul, Ganjali, Mohammed M, Walker, Roderick B
- Authors: Mohammadi, Ali , Alizadeh, Taher , Dinarvand, Rassoul , Ganjali, Mohammed M , Walker, Roderick B
- Date: 2009
- Language: English
- Type: Article
- Identifier: vital:6410 , http://hdl.handle.net/10962/d1006496
- Description: A highly selective methacrylic based molecularly imprinted polymer (MIP) was synthesized and applied for the separation and the pre-concentration of salbutamol in urine samples. Spectrophotometric determination of salbutamol was achieved using 2,6-dichloroquinone chlorimide as colorimetric reagent. The detection limit of the method was ca. 13 ng/mL in urine after pre-concentration of the samples by MIP-SPE andanalysis with an optimized and sensitive spectrophotometric method. The linear dynamic range for salbutamol determination in urine was 0.04-0.75 μg mL-1. The recovery for the affinity based solid-phase extraction (SPE) with the MIP was more than 96 %.
- Full Text:
- Date Issued: 2009
- Authors: Mohammadi, Ali , Alizadeh, Taher , Dinarvand, Rassoul , Ganjali, Mohammed M , Walker, Roderick B
- Date: 2009
- Language: English
- Type: Article
- Identifier: vital:6410 , http://hdl.handle.net/10962/d1006496
- Description: A highly selective methacrylic based molecularly imprinted polymer (MIP) was synthesized and applied for the separation and the pre-concentration of salbutamol in urine samples. Spectrophotometric determination of salbutamol was achieved using 2,6-dichloroquinone chlorimide as colorimetric reagent. The detection limit of the method was ca. 13 ng/mL in urine after pre-concentration of the samples by MIP-SPE andanalysis with an optimized and sensitive spectrophotometric method. The linear dynamic range for salbutamol determination in urine was 0.04-0.75 μg mL-1. The recovery for the affinity based solid-phase extraction (SPE) with the MIP was more than 96 %.
- Full Text:
- Date Issued: 2009
The evaluation of Eudragit microcapsules manufactured by solvent evaporation using USP Apparatus 1
- Khamanga, Sandile M, Parfitt, Natalie R, Nyamuzhiwa, Tsitsi, Haidula, Hendrina, Walker, Roderick B
- Authors: Khamanga, Sandile M , Parfitt, Natalie R , Nyamuzhiwa, Tsitsi , Haidula, Hendrina , Walker, Roderick B
- Date: 2009
- Language: English
- Type: text , Article
- Identifier: vital:6389 , http://hdl.handle.net/10962/d1006310
- Description: The objectives of this study were to prepare microcapsules containing verapamil and propranolol and to evaluate the kinetics and mechanism of drug release from the microcapsules using USP Apparatus 1. The effects of polymer concentration and polymer type on the cumulative amount of drug released were evaluated. The microcapsules were manufactured using Eudragit RS and RL polymers by solvent evaporation with the ultimate aim of prolonging drug release. Twenty-four formulations were prepared using different drug/polymer ratios. The effects of polymer type and polymer/drug ratios on the size, flow properties, surface morphology, and the release characteristics of the microcapsules were examined. The effects of drug inclusion methods on drug loading, encapsulation efficiency, and release properties of the complex microcapsules were also investigated. The formulations containing drug/polymer ratio 1:4 (w/w) were the most appropriate with respect to encapsulation efficiency (70%), flow properties (HR = 1.2), drug loading (15–20%), and drug release characteristics, in all cases. The release kinetics from the different formulations followed mainly a diffusion-controlled mechanism.
- Full Text:
- Date Issued: 2009
- Authors: Khamanga, Sandile M , Parfitt, Natalie R , Nyamuzhiwa, Tsitsi , Haidula, Hendrina , Walker, Roderick B
- Date: 2009
- Language: English
- Type: text , Article
- Identifier: vital:6389 , http://hdl.handle.net/10962/d1006310
- Description: The objectives of this study were to prepare microcapsules containing verapamil and propranolol and to evaluate the kinetics and mechanism of drug release from the microcapsules using USP Apparatus 1. The effects of polymer concentration and polymer type on the cumulative amount of drug released were evaluated. The microcapsules were manufactured using Eudragit RS and RL polymers by solvent evaporation with the ultimate aim of prolonging drug release. Twenty-four formulations were prepared using different drug/polymer ratios. The effects of polymer type and polymer/drug ratios on the size, flow properties, surface morphology, and the release characteristics of the microcapsules were examined. The effects of drug inclusion methods on drug loading, encapsulation efficiency, and release properties of the complex microcapsules were also investigated. The formulations containing drug/polymer ratio 1:4 (w/w) were the most appropriate with respect to encapsulation efficiency (70%), flow properties (HR = 1.2), drug loading (15–20%), and drug release characteristics, in all cases. The release kinetics from the different formulations followed mainly a diffusion-controlled mechanism.
- Full Text:
- Date Issued: 2009
Shoppers Drug Mart or poachers Drug Mart?
- Attaran, Amir, Walker, Roderick B
- Authors: Attaran, Amir , Walker, Roderick B
- Date: 2008
- Language: English
- Type: Article
- Identifier: vital:6346 , http://hdl.handle.net/10962/d1006018
- Description: [From the text]: Shoppers Drug Mart (Pharmaprix in Quebec) is a familiar Canadian institution. Its 1000 stores dot the landscape; no pharmacy chain is larger. In many Canadian communities, the corporation's well-staffed local franchises give patients quality care. However, in South Africa, the same corporation is potentially contributing to a public health disaster. In 2005, 2006 and twice in 2007, it has dispatched recruiters to that country, with the mission of plucking pharmacists from a continent that has far too few for its needs. Shoppers Drug Mart promises 6-figure salaries and help to establish a brilliant career in Canada. The carrot, and the helping hand holding it, are huge.
- Full Text:
- Date Issued: 2008
- Authors: Attaran, Amir , Walker, Roderick B
- Date: 2008
- Language: English
- Type: Article
- Identifier: vital:6346 , http://hdl.handle.net/10962/d1006018
- Description: [From the text]: Shoppers Drug Mart (Pharmaprix in Quebec) is a familiar Canadian institution. Its 1000 stores dot the landscape; no pharmacy chain is larger. In many Canadian communities, the corporation's well-staffed local franchises give patients quality care. However, in South Africa, the same corporation is potentially contributing to a public health disaster. In 2005, 2006 and twice in 2007, it has dispatched recruiters to that country, with the mission of plucking pharmacists from a continent that has far too few for its needs. Shoppers Drug Mart promises 6-figure salaries and help to establish a brilliant career in Canada. The carrot, and the helping hand holding it, are huge.
- Full Text:
- Date Issued: 2008
Should active recruitment of health workers from sub-Saharan Africa be viewed as a crime?
- Mills, E J, Schabas, W A, Volmink, J, Walker, Roderick B, Ford, N, Katabira, E, Anema, A, Joffres, M, Cahn, P, Montaner, J
- Authors: Mills, E J , Schabas, W A , Volmink, J , Walker, Roderick B , Ford, N , Katabira, E , Anema, A , Joffres, M , Cahn, P , Montaner, J
- Date: 2008
- Language: English
- Type: Article
- Identifier: vital:6392 , http://hdl.handle.net/10962/d1006314
- Description: (Conclusion) When the international community permits for-profit companies to actively entice overworked and often underpaid workers away from the most vulnerable populations, it is contributing to the deterioration of essential health-care delivery. Improvement of the health of the world’s poor is a challenge that the international community is failing to adequately address. Current international treaties and commitments are severely compromised if we are unwilling to adhere to their principles and prevent obvious harms to poor people. Clear, enforced regulation is needed to prevent recruitment companies from enticing health workers away from their local work, and developed countries should adequately compensate less-developed countries for the human resources they have lost and continue to lose.
- Full Text:
- Date Issued: 2008
- Authors: Mills, E J , Schabas, W A , Volmink, J , Walker, Roderick B , Ford, N , Katabira, E , Anema, A , Joffres, M , Cahn, P , Montaner, J
- Date: 2008
- Language: English
- Type: Article
- Identifier: vital:6392 , http://hdl.handle.net/10962/d1006314
- Description: (Conclusion) When the international community permits for-profit companies to actively entice overworked and often underpaid workers away from the most vulnerable populations, it is contributing to the deterioration of essential health-care delivery. Improvement of the health of the world’s poor is a challenge that the international community is failing to adequately address. Current international treaties and commitments are severely compromised if we are unwilling to adhere to their principles and prevent obvious harms to poor people. Clear, enforced regulation is needed to prevent recruitment companies from enticing health workers away from their local work, and developed countries should adequately compensate less-developed countries for the human resources they have lost and continue to lose.
- Full Text:
- Date Issued: 2008
Study of the formation of artifacts following Dichloromethane reaction with some nitrogenous drugs
- Mohammadi, Ali, Amini, Mohsen, Hamedani, Moteza P, Torkabadi, Hossein H, Walker, Roderick B
- Authors: Mohammadi, Ali , Amini, Mohsen , Hamedani, Moteza P , Torkabadi, Hossein H , Walker, Roderick B
- Date: 2008
- Language: English
- Type: Article
- Identifier: vital:6409 , http://hdl.handle.net/10962/d1006495
- Description: In this work, the quaternization reaction of some nitrogenous drugs in dichloromethane under stress condition and room temperature at different times are studied. Under these conditions, drug-chloromethochloride adducts or artifacts were found to be formed for clozapine, ofloxacin and olanzapine. The structures of the resultant adducts were elucidated using 1H NMR spectroscopy. In addition, the amount of intact drug was determined using in-house validated HPLC methods with UV detection.
- Full Text:
- Date Issued: 2008
- Authors: Mohammadi, Ali , Amini, Mohsen , Hamedani, Moteza P , Torkabadi, Hossein H , Walker, Roderick B
- Date: 2008
- Language: English
- Type: Article
- Identifier: vital:6409 , http://hdl.handle.net/10962/d1006495
- Description: In this work, the quaternization reaction of some nitrogenous drugs in dichloromethane under stress condition and room temperature at different times are studied. Under these conditions, drug-chloromethochloride adducts or artifacts were found to be formed for clozapine, ofloxacin and olanzapine. The structures of the resultant adducts were elucidated using 1H NMR spectroscopy. In addition, the amount of intact drug was determined using in-house validated HPLC methods with UV detection.
- Full Text:
- Date Issued: 2008
A stability-indicating high performance liquid chromatographic (HPLC) assay for the simultaneous determination of atorvastatin and amlodipine in commercial tablets
- Mohammadi, Ali, Rezanour, N, Ansari Dogaheh, M, Ghorbani Bidkorbeh, F, Hashem, M, Walker, Roderick B
- Authors: Mohammadi, Ali , Rezanour, N , Ansari Dogaheh, M , Ghorbani Bidkorbeh, F , Hashem, M , Walker, Roderick B
- Date: 2007
- Language: English
- Type: Article
- Identifier: vital:6403 , http://hdl.handle.net/10962/d1006340
- Description: A simple, rapid, precise and accurate isocratic reversed-phase stability-indicating HPLC method was developed and validated for the simultaneous determination of atorvastatin (AT) and amlodipine (AM) in commercial tablets. The method has shown adequate separation for AM, AT from their associated main impurities and their degradation products. Separation was achieved on a Perfectsil® Target ODS-3, 5 μm, 250 mm × 4.6 mm i.d. column using a mobile phase consisting of acetonitrile–0.025 M NaH2PO4 buffer (pH 4.5) (55:45, v/v) at a flow rate of 1 ml/min and UV detection at 237 nm. The drugs were subjected to oxidation, hydrolysis, photolysis and heat to apply stress conditions. The linearity of the proposed method was investigated in the range of 2–30 μg/ml (r = 0.9994) for AT and 1–20 μg/ml (r = 0.9993) for AM. The limits of detection were 0.65 μg/ml and 0.35 μg/ml for AT and AM, respectively. The limits of quantitation were 2 μg/ml and 1 μg/ml for AT and AM, respectively. Degradation products produced as a result of stress studies did not interfere with the detection of AT and AM and the assay can thus be considered stability-indicating.
- Full Text:
- Date Issued: 2007
- Authors: Mohammadi, Ali , Rezanour, N , Ansari Dogaheh, M , Ghorbani Bidkorbeh, F , Hashem, M , Walker, Roderick B
- Date: 2007
- Language: English
- Type: Article
- Identifier: vital:6403 , http://hdl.handle.net/10962/d1006340
- Description: A simple, rapid, precise and accurate isocratic reversed-phase stability-indicating HPLC method was developed and validated for the simultaneous determination of atorvastatin (AT) and amlodipine (AM) in commercial tablets. The method has shown adequate separation for AM, AT from their associated main impurities and their degradation products. Separation was achieved on a Perfectsil® Target ODS-3, 5 μm, 250 mm × 4.6 mm i.d. column using a mobile phase consisting of acetonitrile–0.025 M NaH2PO4 buffer (pH 4.5) (55:45, v/v) at a flow rate of 1 ml/min and UV detection at 237 nm. The drugs were subjected to oxidation, hydrolysis, photolysis and heat to apply stress conditions. The linearity of the proposed method was investigated in the range of 2–30 μg/ml (r = 0.9994) for AT and 1–20 μg/ml (r = 0.9993) for AM. The limits of detection were 0.65 μg/ml and 0.35 μg/ml for AT and AM, respectively. The limits of quantitation were 2 μg/ml and 1 μg/ml for AT and AM, respectively. Degradation products produced as a result of stress studies did not interfere with the detection of AT and AM and the assay can thus be considered stability-indicating.
- Full Text:
- Date Issued: 2007
The comparison of in vitro release methods for the evaluation of oxytocin release from Pluronic® F127 parenteral formulations
- Chaibva, Faith A, Walker, Roderick B
- Authors: Chaibva, Faith A , Walker, Roderick B
- Date: 2007
- Language: English
- Type: Article
- Identifier: vital:6351 , http://hdl.handle.net/10962/d1006033
- Description: The objective of these studies was to develop a discriminatory in vitro release test for assessing formulation factors that may affect oxytocin (OT) release during formulation development studies of a Pluronic® F127 OT in situ gel-forming parenteral dosage form. An appropriate release assessment method should be able to discriminate between the performance of different formulation compositions (1, 2), and this was the primary criterion used for selection of an appropriate test procedure during the test method development process. ANOVA and the difference (f1) and similarity (f2)factors were used to evaluate the discriminatory behavior of different test methods that were investigated in these studies. The in vitro release tests that were investigated included the use of USP Apparatus 1, 2, and 3; a dialysis bag in USP Apparatus 2; and a membrane-less diffusion method. It was concluded that the use of USP Apparatus 3 was best able to discriminate between OT release for the different formulations tested. USP Apparatus 3 was thus considered the most suitable in vitro release test apparatus for studying formulation factors affecting OT release during the development of a parenteral dosage form prepared using Pluronic® F127.
- Full Text:
- Date Issued: 2007
- Authors: Chaibva, Faith A , Walker, Roderick B
- Date: 2007
- Language: English
- Type: Article
- Identifier: vital:6351 , http://hdl.handle.net/10962/d1006033
- Description: The objective of these studies was to develop a discriminatory in vitro release test for assessing formulation factors that may affect oxytocin (OT) release during formulation development studies of a Pluronic® F127 OT in situ gel-forming parenteral dosage form. An appropriate release assessment method should be able to discriminate between the performance of different formulation compositions (1, 2), and this was the primary criterion used for selection of an appropriate test procedure during the test method development process. ANOVA and the difference (f1) and similarity (f2)factors were used to evaluate the discriminatory behavior of different test methods that were investigated in these studies. The in vitro release tests that were investigated included the use of USP Apparatus 1, 2, and 3; a dialysis bag in USP Apparatus 2; and a membrane-less diffusion method. It was concluded that the use of USP Apparatus 3 was best able to discriminate between OT release for the different formulations tested. USP Apparatus 3 was thus considered the most suitable in vitro release test apparatus for studying formulation factors affecting OT release during the development of a parenteral dosage form prepared using Pluronic® F127.
- Full Text:
- Date Issued: 2007
The effects of buffer molarity, agitation rate and mesh size on verapamil release from modified release mini-tablets using USP Apparatus 3
- Khamanga, Sandile M, Walker, Roderick B
- Authors: Khamanga, Sandile M , Walker, Roderick B
- Date: 2007
- Language: English
- Type: text , Article
- Identifier: vital:6386 , http://hdl.handle.net/10962/d1006307
- Description: The effects of agitation rate, buffer molarity,and mesh size on the dissolution rate of verapamil hydrochloride from sustained release matrix tablets were studied using USP Apparatus 3. Eudragit® and Carbopol® were used as rate-retarding polymers in tablets prepared by wet granulation.The study was conducted to determine whether the drugs exhibit similar release characteristics when tested under the same dissolution conditions. It was found that the dissolution rate of verapamil hydrochloride was affected by the variables assessed in these studies.
- Full Text:
- Date Issued: 2007
- Authors: Khamanga, Sandile M , Walker, Roderick B
- Date: 2007
- Language: English
- Type: text , Article
- Identifier: vital:6386 , http://hdl.handle.net/10962/d1006307
- Description: The effects of agitation rate, buffer molarity,and mesh size on the dissolution rate of verapamil hydrochloride from sustained release matrix tablets were studied using USP Apparatus 3. Eudragit® and Carbopol® were used as rate-retarding polymers in tablets prepared by wet granulation.The study was conducted to determine whether the drugs exhibit similar release characteristics when tested under the same dissolution conditions. It was found that the dissolution rate of verapamil hydrochloride was affected by the variables assessed in these studies.
- Full Text:
- Date Issued: 2007
A stability-indicating high performance liquid chromatographic assay for the determination of orlistat in capsules
- Mohammadi, Ali, Haririan, I, Rezanour, I, Ghiasi, L, Walker, Roderick B
- Authors: Mohammadi, Ali , Haririan, I , Rezanour, I , Ghiasi, L , Walker, Roderick B
- Date: 2006
- Language: English
- Type: Article , text
- Identifier: vital:6407 , http://hdl.handle.net/10962/d1006480
- Description: A stability-indicating HPLC method was developed and validated for the quantitative determination of orlistat in capsule dosage forms. An isocratic separation was achieved using a Perfectsil® target ODS-3, 250 mm × 4.6 mm i.d., 5 µm particle size column with a flow rate of 0.7 ml/min and using a UV detector to monitor the eluate at 210 nm. The mobile phase consisted of methanol:acetonitrile:trifluoroacetic acid (82.5:17.5:0.01, v/v/v). The drug was subjected oxidation, hydrolysis, photolysis and heat to apply stress conditions. Complete separation was achieved for the parent compound and all degradation products in an overall analytical run time of approximately 15 min with the parent compound orlistat eluting at approximately 9 min. The method was linear over the concentration range of 0.02–0.75 mg/ml (r = 0.9998) with a limit of detection and quantitation 0.006 and 0.02 mg/ml, respectively. The method has the requisite accuracy, selectivity, sensitivity and precision to assay orlistat in capsules. Degradation products resulting from the stress studies did not interfere with the detection of orlistat and the assay is thus stability-indicating.
- Full Text:
- Date Issued: 2006
- Authors: Mohammadi, Ali , Haririan, I , Rezanour, I , Ghiasi, L , Walker, Roderick B
- Date: 2006
- Language: English
- Type: Article , text
- Identifier: vital:6407 , http://hdl.handle.net/10962/d1006480
- Description: A stability-indicating HPLC method was developed and validated for the quantitative determination of orlistat in capsule dosage forms. An isocratic separation was achieved using a Perfectsil® target ODS-3, 250 mm × 4.6 mm i.d., 5 µm particle size column with a flow rate of 0.7 ml/min and using a UV detector to monitor the eluate at 210 nm. The mobile phase consisted of methanol:acetonitrile:trifluoroacetic acid (82.5:17.5:0.01, v/v/v). The drug was subjected oxidation, hydrolysis, photolysis and heat to apply stress conditions. Complete separation was achieved for the parent compound and all degradation products in an overall analytical run time of approximately 15 min with the parent compound orlistat eluting at approximately 9 min. The method was linear over the concentration range of 0.02–0.75 mg/ml (r = 0.9998) with a limit of detection and quantitation 0.006 and 0.02 mg/ml, respectively. The method has the requisite accuracy, selectivity, sensitivity and precision to assay orlistat in capsules. Degradation products resulting from the stress studies did not interfere with the detection of orlistat and the assay is thus stability-indicating.
- Full Text:
- Date Issued: 2006
A stability-indicating high performance liquid chromatographic assay for the determination of orlistat in capsules
- Mohammadi, Ali, Haririan, I, Rezanour, Nasrin, Ghiasi, L, Walker, Roderick B
- Authors: Mohammadi, Ali , Haririan, I , Rezanour, Nasrin , Ghiasi, L , Walker, Roderick B
- Date: 2006
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184267 , vital:44195 , xlink:href="https://doi.org/10.1016/j.chroma.2006.03.038"
- Description: A stability-indicating HPLC method was developed and validated for the quantitative determination of orlistat in capsule dosage forms. An isocratic separation was achieved using a Perfectsil® target ODS-3, 250 mm × 4.6 mm i.d., 5 μm particle size column with a flow rate of 0.7 ml/min and using a UV detector to monitor the eluate at 210 nm. The mobile phase consisted of methanol:acetonitrile:trifluoroacetic acid (82.5:17.5:0.01, v/v/v). The drug was subjected oxidation, hydrolysis, photolysis and heat to apply stress conditions. Complete separation was achieved for the parent compound and all degradation products in an overall analytical run time of approximately 15 min with the parent compound orlistat eluting at approximately 9 min. The method was linear over the concentration range of 0.02–0.75 mg/ml (r = 0.9998) with a limit of detection and quantitation 0.006 and 0.02 mg/ml, respectively. The method has the requisite accuracy, selectivity, sensitivity and precision to assay orlistat in capsules. Degradation products resulting from the stress studies did not interfere with the detection of orlistat and the assay is thus stability-indicating.
- Full Text:
- Date Issued: 2006
- Authors: Mohammadi, Ali , Haririan, I , Rezanour, Nasrin , Ghiasi, L , Walker, Roderick B
- Date: 2006
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184267 , vital:44195 , xlink:href="https://doi.org/10.1016/j.chroma.2006.03.038"
- Description: A stability-indicating HPLC method was developed and validated for the quantitative determination of orlistat in capsule dosage forms. An isocratic separation was achieved using a Perfectsil® target ODS-3, 250 mm × 4.6 mm i.d., 5 μm particle size column with a flow rate of 0.7 ml/min and using a UV detector to monitor the eluate at 210 nm. The mobile phase consisted of methanol:acetonitrile:trifluoroacetic acid (82.5:17.5:0.01, v/v/v). The drug was subjected oxidation, hydrolysis, photolysis and heat to apply stress conditions. Complete separation was achieved for the parent compound and all degradation products in an overall analytical run time of approximately 15 min with the parent compound orlistat eluting at approximately 9 min. The method was linear over the concentration range of 0.02–0.75 mg/ml (r = 0.9998) with a limit of detection and quantitation 0.006 and 0.02 mg/ml, respectively. The method has the requisite accuracy, selectivity, sensitivity and precision to assay orlistat in capsules. Degradation products resulting from the stress studies did not interfere with the detection of orlistat and the assay is thus stability-indicating.
- Full Text:
- Date Issued: 2006
Bioequivalence assessment of generic products an innovative South African approach
- Walker, Roderick B, Kanfer, Isadore, Skinner, Michael F
- Authors: Walker, Roderick B , Kanfer, Isadore , Skinner, Michael F
- Date: 2006
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184256 , vital:44194 , xlink:href="https://doi.org/10.1080/10601330500534014"
- Description: Concurrent with the implementation of new legislation mandating Generic Substitution in South Africa, a new set of guidelines for bioavailability and bioequivalence have been published. Since one of the main objectives of the new legislation in South Africa relating to Generic Substitution is to ensure that medicines of high quality, safety, and efficacy are made more accessible and more affordable to the wider public, the need to speed up approval of such multi-source products has become a regulatory priority. In order to facilitate this process, various bioequivalence issues have been addressed including important issues such as the acceptance criteria and associated bioequivalence intervals, use of a foreign reference product and the issue of assessing highly variable drugs (HVDs). In addition, dispensations have been made with respect to food effect assessment and variability relating to genetic polymorphism in drug metabolism (genotyping/phenotyping). Furthermore, the use of “old” biostudies submitted in support of an application is subject to expiry date. Acceptance of appropriate data requires that specific criteria such as Cmax and AUC, in addition to the usual considerations, also meet the limits specified by the particular registration authority of the country where such products are intended to be marketed. Generally, these limits require that the 90% confidence interval (CI) for AUC and Cmax test/reference ratios lies within the acceptance interval of 0.80–1.25 calculated using log-transformed data. While such acceptance criteria are, in general, ubiquitous, some differences in acceptance criteria do exist between various countries. The new guidelines for bioavailability/bioequivalence studies developed by the South African regulatory authority, the Medicines Control Council (MCC), makes provision for highly variable drugs and the use of a non-South African reference product. The MCC requires that the acceptance criterion for Cmax ratios be set at 0.75–1.33 while maintaining AUC ratios at 0.80–1.25 using a 90% CI. Furthermore, provision is made to apply scaling based on average bioequivalence assessment and, as an interim measure, consideration has also been given to the use of a foreign reference product provided that equivalence between that product and the innovator product currently available on the South African market can be shown using in vitro testing.
- Full Text:
- Date Issued: 2006
- Authors: Walker, Roderick B , Kanfer, Isadore , Skinner, Michael F
- Date: 2006
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184256 , vital:44194 , xlink:href="https://doi.org/10.1080/10601330500534014"
- Description: Concurrent with the implementation of new legislation mandating Generic Substitution in South Africa, a new set of guidelines for bioavailability and bioequivalence have been published. Since one of the main objectives of the new legislation in South Africa relating to Generic Substitution is to ensure that medicines of high quality, safety, and efficacy are made more accessible and more affordable to the wider public, the need to speed up approval of such multi-source products has become a regulatory priority. In order to facilitate this process, various bioequivalence issues have been addressed including important issues such as the acceptance criteria and associated bioequivalence intervals, use of a foreign reference product and the issue of assessing highly variable drugs (HVDs). In addition, dispensations have been made with respect to food effect assessment and variability relating to genetic polymorphism in drug metabolism (genotyping/phenotyping). Furthermore, the use of “old” biostudies submitted in support of an application is subject to expiry date. Acceptance of appropriate data requires that specific criteria such as Cmax and AUC, in addition to the usual considerations, also meet the limits specified by the particular registration authority of the country where such products are intended to be marketed. Generally, these limits require that the 90% confidence interval (CI) for AUC and Cmax test/reference ratios lies within the acceptance interval of 0.80–1.25 calculated using log-transformed data. While such acceptance criteria are, in general, ubiquitous, some differences in acceptance criteria do exist between various countries. The new guidelines for bioavailability/bioequivalence studies developed by the South African regulatory authority, the Medicines Control Council (MCC), makes provision for highly variable drugs and the use of a non-South African reference product. The MCC requires that the acceptance criterion for Cmax ratios be set at 0.75–1.33 while maintaining AUC ratios at 0.80–1.25 using a 90% CI. Furthermore, provision is made to apply scaling based on average bioequivalence assessment and, as an interim measure, consideration has also been given to the use of a foreign reference product provided that equivalence between that product and the innovator product currently available on the South African market can be shown using in vitro testing.
- Full Text:
- Date Issued: 2006
Development and validation of a stability-indicating analytical method for the quantitation of oxytocin in pharmaceutical dosage forms
- Chaibva, Faith A, Walker, Roderick B
- Authors: Chaibva, Faith A , Walker, Roderick B
- Date: 2006
- Language: English
- Type: Article
- Identifier: vital:6349 , http://hdl.handle.net/10962/d1006030
- Description: A single stability-indicating assay for oxytocin (OT) in pharmaceutical dosage forms using gradient elution over 21 min has been reported in the literature. Furthermore, published and compendial methods for the analysis of OT containing dosage forms also involve using HPLC with gradient elution and complicated mobile phases that include hydrophobic ion pairing agents. A simple isocratic and stability-indicating assay was developed and validated. The conditions are as follows, column: Phenomenex® C18 Hypersil, 5 μm packing, 4.6 mm × 150 mm with acetonitrile–phosphate buffer (pH 5; 0.08 M) (20:80) as the mobile phase with UV detection at 220 nm The method was found to be specific for OT in the presence of degradation products and chlorbutol (preservative) with an overall analytical run time of 16 min. Accuracy was determined to be 0.77–1.18% bias for all samples tested. Intra-assay precision (repeatability) was found to be 0.22–1.04%R.S.D. while the inter-day precision (intermediate precision) was found to be 1.27–1.68%R.S.D. for the samples studied. The calibration curve was found to be linear with the equation y = 1.81x + 0.02 and a linear regression coefficient of 0.9991 over the range 0.4–12.0 IU/ml. The LOD and the LOQ were determined to be 0.1 and 0.4 IU/ml, respectively. Syntocinon®, a commercially available dosage form of OT was assayed resulting in 100.5–106.6% recovery of the label claim and an average of 10.04 IU/ml.
- Full Text:
- Date Issued: 2006
- Authors: Chaibva, Faith A , Walker, Roderick B
- Date: 2006
- Language: English
- Type: Article
- Identifier: vital:6349 , http://hdl.handle.net/10962/d1006030
- Description: A single stability-indicating assay for oxytocin (OT) in pharmaceutical dosage forms using gradient elution over 21 min has been reported in the literature. Furthermore, published and compendial methods for the analysis of OT containing dosage forms also involve using HPLC with gradient elution and complicated mobile phases that include hydrophobic ion pairing agents. A simple isocratic and stability-indicating assay was developed and validated. The conditions are as follows, column: Phenomenex® C18 Hypersil, 5 μm packing, 4.6 mm × 150 mm with acetonitrile–phosphate buffer (pH 5; 0.08 M) (20:80) as the mobile phase with UV detection at 220 nm The method was found to be specific for OT in the presence of degradation products and chlorbutol (preservative) with an overall analytical run time of 16 min. Accuracy was determined to be 0.77–1.18% bias for all samples tested. Intra-assay precision (repeatability) was found to be 0.22–1.04%R.S.D. while the inter-day precision (intermediate precision) was found to be 1.27–1.68%R.S.D. for the samples studied. The calibration curve was found to be linear with the equation y = 1.81x + 0.02 and a linear regression coefficient of 0.9991 over the range 0.4–12.0 IU/ml. The LOD and the LOQ were determined to be 0.1 and 0.4 IU/ml, respectively. Syntocinon®, a commercially available dosage form of OT was assayed resulting in 100.5–106.6% recovery of the label claim and an average of 10.04 IU/ml.
- Full Text:
- Date Issued: 2006
Evaluation of rate of swelling and erosion of verapamil (VRP) sustained-release matrix tablets
- Khamanga, Sandile M, Walker, Roderick B
- Authors: Khamanga, Sandile M , Walker, Roderick B
- Date: 2006
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184232 , vital:44192 , xlink:href="https://doi.org/10.1080/03639040600599822"
- Description: Tablets manufactured in-house were compared to a marketed sustained-release product of verapamil to investigate the rate of hydration, erosion, and drug-release mechanism by measuring the wet and subsequent dry weights of the products. Swelling and erosion rates depended on the polymer and granulating fluid used, which ultimately pointed to their permeability characteristics. Erosion rate of the marketed product was highest, which suggests that the gel layer that formed around these tablets was weak as opposed to the robust and resistant layers of test products. Anomalous and near zero-order transport mechanisms were dominant in tests and commercial product, respectively.
- Full Text:
- Date Issued: 2006
- Authors: Khamanga, Sandile M , Walker, Roderick B
- Date: 2006
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184232 , vital:44192 , xlink:href="https://doi.org/10.1080/03639040600599822"
- Description: Tablets manufactured in-house were compared to a marketed sustained-release product of verapamil to investigate the rate of hydration, erosion, and drug-release mechanism by measuring the wet and subsequent dry weights of the products. Swelling and erosion rates depended on the polymer and granulating fluid used, which ultimately pointed to their permeability characteristics. Erosion rate of the marketed product was highest, which suggests that the gel layer that formed around these tablets was weak as opposed to the robust and resistant layers of test products. Anomalous and near zero-order transport mechanisms were dominant in tests and commercial product, respectively.
- Full Text:
- Date Issued: 2006
Generic substitution: the use of medicinal products containing different salts and implications for safety and efficacy
- Verbeeck, R K, Kanfer, Isadore, Walker, Roderick B
- Authors: Verbeeck, R K , Kanfer, Isadore , Walker, Roderick B
- Date: 2006
- Language: English
- Type: text , Article
- Identifier: vital:6445 , http://hdl.handle.net/10962/d1006632
- Description: In their quest to gain early entry of new generic products into the market prior to patent expiration, one of the strategies pursued by generic drug product manufacturers is to incorporate different salts of an approved active pharmaceutical ingredient (API) in a brand company's marketed dosage form and subject such dosage forms to bioequivalence assessment. These initiatives present challenges to regulatory authorities where the decision to approve bioequivalent products containing such pharmaceutical alternatives must be considered in the light of safety and efficacy, and more particularly, with respect to their substitutability. This article describes the various issues and contentions associated with the concept of pharmaceutical alternatives, specifically with respect to the uses of different salts and the implications for safety, efficacy and generic substitution.
- Full Text:
- Date Issued: 2006
- Authors: Verbeeck, R K , Kanfer, Isadore , Walker, Roderick B
- Date: 2006
- Language: English
- Type: text , Article
- Identifier: vital:6445 , http://hdl.handle.net/10962/d1006632
- Description: In their quest to gain early entry of new generic products into the market prior to patent expiration, one of the strategies pursued by generic drug product manufacturers is to incorporate different salts of an approved active pharmaceutical ingredient (API) in a brand company's marketed dosage form and subject such dosage forms to bioequivalence assessment. These initiatives present challenges to regulatory authorities where the decision to approve bioequivalent products containing such pharmaceutical alternatives must be considered in the light of safety and efficacy, and more particularly, with respect to their substitutability. This article describes the various issues and contentions associated with the concept of pharmaceutical alternatives, specifically with respect to the uses of different salts and the implications for safety, efficacy and generic substitution.
- Full Text:
- Date Issued: 2006
Spotlight on research: 50 years of Pharmaceutical Sciences Research Excellence Faculty of Pharmacy Rhodes University
- Authors: Walker, Roderick B
- Date: 2006
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184243 , vital:44193 , xlink:href="https://hdl.handle.net/10520/EJC81478"
- Description: This year, the Faculty of Pharmacy at Rhodes University is celebrating its 50th Anniversary. Over 2000 BPharm, 33 BSc honours, 65 MSc and 27 PhD degrees have been conferred since the Faculty’s inception. The diverse research activities and dedicated academic staff have ensured that the Faculty of Pharmacy has high visibility with respect to research outputs, as is evidenced by the appointment of various members of staff to national and international research, regulatory and professional committees, as well as to serving on the editorial boards of a number of international journals. In addition, staff regularly publish in international and local peer-reviewed journals and present their research findings at international and local conferences.
- Full Text:
- Date Issued: 2006
- Authors: Walker, Roderick B
- Date: 2006
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184243 , vital:44193 , xlink:href="https://hdl.handle.net/10520/EJC81478"
- Description: This year, the Faculty of Pharmacy at Rhodes University is celebrating its 50th Anniversary. Over 2000 BPharm, 33 BSc honours, 65 MSc and 27 PhD degrees have been conferred since the Faculty’s inception. The diverse research activities and dedicated academic staff have ensured that the Faculty of Pharmacy has high visibility with respect to research outputs, as is evidenced by the appointment of various members of staff to national and international research, regulatory and professional committees, as well as to serving on the editorial boards of a number of international journals. In addition, staff regularly publish in international and local peer-reviewed journals and present their research findings at international and local conferences.
- Full Text:
- Date Issued: 2006
An LC-MS-MS method for the determination of cyclizine in human serum
- Mohammadi, Ali, Kanfer, Isadore, Sewram, V, Walker, Roderick B
- Authors: Mohammadi, Ali , Kanfer, Isadore , Sewram, V , Walker, Roderick B
- Date: 2005
- Language: English
- Type: Article
- Identifier: vital:6408 , http://hdl.handle.net/10962/d1006481
- Description: Cyclizine is a piperazine derivative with anti-emetic activity that is useful in the prevention and treatment of nausea and vomiting associated with motion sickness. A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method is presented for the quantitation of cyclizine in serum. Sample pretreatment involved liquid-liquid extraction of 200 μl of serum with dichloromethane after the addition of 100 μl each of ammonium hydroxide and internal standard solutions. The extracts were analyzed by HPLC on a Luna ® C18 reversed-phase column and an ion-trap mass spectrometer with an electrospray interface. A limit of detection of 1 ng/ml was determined which allowed for the reliable measurement of cyclizine in the serum of human subjects. The method was found to be linear over the calibration range of 2.5-100 ng/ml. The applicability of this method was demonstrated by the analysis of serum obtained from a human volunteer following administration of a single 50 mg cyclizine hydrochloride tablet. The reported method was observed to have the necessary sensitivity, selectivity, precision and accuracy for monitoring cyclizine concentrations in human subjects following oral administration.
- Full Text:
- Date Issued: 2005
- Authors: Mohammadi, Ali , Kanfer, Isadore , Sewram, V , Walker, Roderick B
- Date: 2005
- Language: English
- Type: Article
- Identifier: vital:6408 , http://hdl.handle.net/10962/d1006481
- Description: Cyclizine is a piperazine derivative with anti-emetic activity that is useful in the prevention and treatment of nausea and vomiting associated with motion sickness. A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method is presented for the quantitation of cyclizine in serum. Sample pretreatment involved liquid-liquid extraction of 200 μl of serum with dichloromethane after the addition of 100 μl each of ammonium hydroxide and internal standard solutions. The extracts were analyzed by HPLC on a Luna ® C18 reversed-phase column and an ion-trap mass spectrometer with an electrospray interface. A limit of detection of 1 ng/ml was determined which allowed for the reliable measurement of cyclizine in the serum of human subjects. The method was found to be linear over the calibration range of 2.5-100 ng/ml. The applicability of this method was demonstrated by the analysis of serum obtained from a human volunteer following administration of a single 50 mg cyclizine hydrochloride tablet. The reported method was observed to have the necessary sensitivity, selectivity, precision and accuracy for monitoring cyclizine concentrations in human subjects following oral administration.
- Full Text:
- Date Issued: 2005
A capillary zone electrophoresis (CZE) method for the determination of cyclizine hydrochloride in tablets and suppositories
- Mohammadi, I, Kanfer, Isadore, Walker, Roderick B
- Authors: Mohammadi, I , Kanfer, Isadore , Walker, Roderick B
- Date: 2004
- Language: English
- Type: Article
- Identifier: vital:6406 , http://hdl.handle.net/10962/d1006479
- Description: Current compendial methods of assay for the analysis of cyclizine tablets involve the use of UV spectrophotometry. Since this is a non-selective technique its application to more complex dosage forms, such as suppositories, is unlikely to be appropriate. There is therefore a need for the development of a highly specific quantitative analytical method, such as high performance liquid chromatography (HPLC) or capillary electrophoresis (CE). The latter technique was chosen in view of some specific advantages over HPLC, such as the use of relatively non-toxic aqueous buffers, as opposed to organic solvents, which obviates the use of expensive HPLC grade solvents making CE more cost effective. Cyclizine was analyzed in 50 mM phosphate buffer (pH 2.3) and run at an applied voltage 25 kV. Detection sensitivity was enhanced by using a wavelength of 200 nm and samples were loaded hydrodynamically onto an uncoated fused-silica capillary (60 cm×50 mm i.d.). Chlorcyclizine was used as the internal standard and resolution of both compounds was achieved in less than 7 min. Stress testing was undertaken in order to investigate the appearance of breakdown products. The method has the requisite accuracy, selectivity, sensitivity and precision to assay cyclizine in tablets and suppositories. Degradation products resulting from the stress studies did not interfere with the detection of cyclizine and the assay is thus stability-indicating.
- Full Text:
- Date Issued: 2004
- Authors: Mohammadi, I , Kanfer, Isadore , Walker, Roderick B
- Date: 2004
- Language: English
- Type: Article
- Identifier: vital:6406 , http://hdl.handle.net/10962/d1006479
- Description: Current compendial methods of assay for the analysis of cyclizine tablets involve the use of UV spectrophotometry. Since this is a non-selective technique its application to more complex dosage forms, such as suppositories, is unlikely to be appropriate. There is therefore a need for the development of a highly specific quantitative analytical method, such as high performance liquid chromatography (HPLC) or capillary electrophoresis (CE). The latter technique was chosen in view of some specific advantages over HPLC, such as the use of relatively non-toxic aqueous buffers, as opposed to organic solvents, which obviates the use of expensive HPLC grade solvents making CE more cost effective. Cyclizine was analyzed in 50 mM phosphate buffer (pH 2.3) and run at an applied voltage 25 kV. Detection sensitivity was enhanced by using a wavelength of 200 nm and samples were loaded hydrodynamically onto an uncoated fused-silica capillary (60 cm×50 mm i.d.). Chlorcyclizine was used as the internal standard and resolution of both compounds was achieved in less than 7 min. Stress testing was undertaken in order to investigate the appearance of breakdown products. The method has the requisite accuracy, selectivity, sensitivity and precision to assay cyclizine in tablets and suppositories. Degradation products resulting from the stress studies did not interfere with the detection of cyclizine and the assay is thus stability-indicating.
- Full Text:
- Date Issued: 2004
6-Hydroxymelatonin protects against cyanide induced oxidative stress in rat brain homogenates
- Maharaj, Deepa S, Walker, Roderick B, Glass, Beverley D, Daya, Santylal
- Authors: Maharaj, Deepa S , Walker, Roderick B , Glass, Beverley D , Daya, Santylal
- Date: 2003
- Language: English
- Type: Article , text
- Identifier: vital:6405 , http://hdl.handle.net/10962/d1006478
- Description: Both 6-hydroxymelatonin and N-acetyl-N-formyl-5-methoxykynurenamine are photodegradants and enzymatic metabolites of melatonin and are known to retain equipotent activity against potassium cyanide-induced superoxide generation compared to melatonin. It is not clear whether one or both of these metabolites is responsible for this effect. The present study therefore investigates the possible manner in which 6-hydroxymelatonin protects against oxidative stress induced by cyanide in rat brain homogenates. We examined the ability of 6-hydroxymelatonin to scavenge KCN-induced superoxide anion generation as well as lipid peroxidation. In addition, we also examined the effect of this indole on lactate dehydrogenase activity (LDH) as well as mitochondrial electron transport using dichlorophenol–indophenol as an electron acceptor. The results of this study show that 6-hydroxymelatonin significantly reduces KCN-induced superoxide anion generation, which is accompanied by a commensurate reduction in lipid peroxidation. Partial reversal of the KCN-induced reduction in mitochondrial electron transport is accompanied by a similar reversal of mitochondrial LDH activity blunted by KCN. It can thus be proposed that 6-hydroxymelatonin is potentially neuroprotective against KCN-induced neurotoxicity.
- Full Text:
- Date Issued: 2003
- Authors: Maharaj, Deepa S , Walker, Roderick B , Glass, Beverley D , Daya, Santylal
- Date: 2003
- Language: English
- Type: Article , text
- Identifier: vital:6405 , http://hdl.handle.net/10962/d1006478
- Description: Both 6-hydroxymelatonin and N-acetyl-N-formyl-5-methoxykynurenamine are photodegradants and enzymatic metabolites of melatonin and are known to retain equipotent activity against potassium cyanide-induced superoxide generation compared to melatonin. It is not clear whether one or both of these metabolites is responsible for this effect. The present study therefore investigates the possible manner in which 6-hydroxymelatonin protects against oxidative stress induced by cyanide in rat brain homogenates. We examined the ability of 6-hydroxymelatonin to scavenge KCN-induced superoxide anion generation as well as lipid peroxidation. In addition, we also examined the effect of this indole on lactate dehydrogenase activity (LDH) as well as mitochondrial electron transport using dichlorophenol–indophenol as an electron acceptor. The results of this study show that 6-hydroxymelatonin significantly reduces KCN-induced superoxide anion generation, which is accompanied by a commensurate reduction in lipid peroxidation. Partial reversal of the KCN-induced reduction in mitochondrial electron transport is accompanied by a similar reversal of mitochondrial LDH activity blunted by KCN. It can thus be proposed that 6-hydroxymelatonin is potentially neuroprotective against KCN-induced neurotoxicity.
- Full Text:
- Date Issued: 2003
An assessment of the efficacy of two lysine microencapsulation techniques to determine the quantitative lysine requirement of the South African abalone, Haliotis midae L
- Shipton, Thomas A, Britz, Peter J, Walker, Roderick B
- Authors: Shipton, Thomas A , Britz, Peter J , Walker, Roderick B
- Date: 2002
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184289 , vital:44197 , xlink:href="https://doi.org/10.1046/j.1365-2095.2002.00204.x"
- Description: The quantification of the essential amino acid requirements of a species is a prerequisite to the formulation of biologically optimized diets. In this study, crystalline L-lysine was used in an attempt to determine the quantitative lysine requirement of juvenile Haliotis midae. Two microencapsulation techniques [gelatine/acacia and cellulose acetate phthalate (CAP)] were used to retard leaching of crystalline L-lysine incorporated into semipurified test diets. An assessment of the efficacy of the encapsulation techniques, revealed that despite effective lysine supplementation, H. midae fed semipurified test diets containing encapsulated crystalline L-lysine failed to promote significant improvements in either growth, feed or protein efficiency (P > 0.05). The failure of the crystalline L-lysine to illicit growth and nutritional responses is discussed.
- Full Text:
- Date Issued: 2002
- Authors: Shipton, Thomas A , Britz, Peter J , Walker, Roderick B
- Date: 2002
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184289 , vital:44197 , xlink:href="https://doi.org/10.1046/j.1365-2095.2002.00204.x"
- Description: The quantification of the essential amino acid requirements of a species is a prerequisite to the formulation of biologically optimized diets. In this study, crystalline L-lysine was used in an attempt to determine the quantitative lysine requirement of juvenile Haliotis midae. Two microencapsulation techniques [gelatine/acacia and cellulose acetate phthalate (CAP)] were used to retard leaching of crystalline L-lysine incorporated into semipurified test diets. An assessment of the efficacy of the encapsulation techniques, revealed that despite effective lysine supplementation, H. midae fed semipurified test diets containing encapsulated crystalline L-lysine failed to promote significant improvements in either growth, feed or protein efficiency (P > 0.05). The failure of the crystalline L-lysine to illicit growth and nutritional responses is discussed.
- Full Text:
- Date Issued: 2002
The identification of the UV degradants of melatonin and their ability to scavenge free radicals
- Maharaj, Deepa S, Anoopkumar-Dukie, Shailendra, Glass, Beverley D, Antunes, Edith M, Lack, Barbara A, Walker, Roderick B, Daya, Santylal
- Authors: Maharaj, Deepa S , Anoopkumar-Dukie, Shailendra , Glass, Beverley D , Antunes, Edith M , Lack, Barbara A , Walker, Roderick B , Daya, Santylal
- Date: 2002
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184303 , vital:44198 , xlink:href="https://doi.org/10.1034/j.1600-079X.2002.01866.x"
- Description: Ultraviolet (UV) light is known to induce the generation of free radicals in biological tissues such as skin. Of these free radicals, the O2–· and particularly the ·OH radical can induce cellular damage including lipid peroxidation. Thus, the use of antioxidants to prevent such damage induced by UV irradiation has received much attention recently. One such antioxidant, which has the potential to be incorporated into sunscreens, is the pineal secretory product melatonin. One of the concerns of using melatonin in sunscreens is its photostability. In the present study, we investigated the photostability of melatonin subjected to UV irradiation. In addition, we used liquid chromatography mass spectrometry (LC-MS) to identify the degradants and we also assessed the ability of the degradants to inhibit O2–· generation as well as lipid peroxidation in rat brain homogenate. The results show that UV irradiation of melatonin (0.1 mg/mL) using a 400-W lamp for 2 hr caused a significant decline of melatonin to 18% of its original concentration after 20 min, with the decline continuing until the melatonin concentration reaches zero at 120 min. The LC-MS results show that the degradants of melatonin are 6-hydroxymelatonin and N1-acetyl-N2-formyl-5-methoxykynurenamine (AFMK). These degradants were able to provide equipotent activity against potassium cyanide (KCN)-induced superoxide generation compared to non-irradiated melatonin. Thus, the study shows that although melatonin is rapidly degraded by UV irradiation, the degradants retain antioxidant activity, making melatonin a likely candidate for inclusion in sunscreens.
- Full Text:
- Date Issued: 2002
- Authors: Maharaj, Deepa S , Anoopkumar-Dukie, Shailendra , Glass, Beverley D , Antunes, Edith M , Lack, Barbara A , Walker, Roderick B , Daya, Santylal
- Date: 2002
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/184303 , vital:44198 , xlink:href="https://doi.org/10.1034/j.1600-079X.2002.01866.x"
- Description: Ultraviolet (UV) light is known to induce the generation of free radicals in biological tissues such as skin. Of these free radicals, the O2–· and particularly the ·OH radical can induce cellular damage including lipid peroxidation. Thus, the use of antioxidants to prevent such damage induced by UV irradiation has received much attention recently. One such antioxidant, which has the potential to be incorporated into sunscreens, is the pineal secretory product melatonin. One of the concerns of using melatonin in sunscreens is its photostability. In the present study, we investigated the photostability of melatonin subjected to UV irradiation. In addition, we used liquid chromatography mass spectrometry (LC-MS) to identify the degradants and we also assessed the ability of the degradants to inhibit O2–· generation as well as lipid peroxidation in rat brain homogenate. The results show that UV irradiation of melatonin (0.1 mg/mL) using a 400-W lamp for 2 hr caused a significant decline of melatonin to 18% of its original concentration after 20 min, with the decline continuing until the melatonin concentration reaches zero at 120 min. The LC-MS results show that the degradants of melatonin are 6-hydroxymelatonin and N1-acetyl-N2-formyl-5-methoxykynurenamine (AFMK). These degradants were able to provide equipotent activity against potassium cyanide (KCN)-induced superoxide generation compared to non-irradiated melatonin. Thus, the study shows that although melatonin is rapidly degraded by UV irradiation, the degradants retain antioxidant activity, making melatonin a likely candidate for inclusion in sunscreens.
- Full Text:
- Date Issued: 2002