PROF. ABUGA, KENNEDY OMONDI

During the five-year period covering 2016-2020, the Drug Analysis and Research Unit (DARU) received and processed 326 drug samples. Of these samples, 32.5% were locally manufactured, 65.7% imported and 1.8% of undeclared origin. Samples were analyzed according to compendial and/or in-house specifications. The overall non-compliance rate was 1.8% (0.6% locally manufactured, 0.9% imported and 0.3% drugs of undeclared origin). Full analytical compliance was recorded with anti-emetics. spasmolytics, antihypertensives, ophthalmics, anti-infectives, analgesics, anti-inflammatory agents, anti-epileptics, nootropics, anaesthetics, respiratory drugs, genitourinary drugs, anticancers, dermatologicals, immunomodulatory drugs, vaccines and excipients. However, one sample each of anti-ulcers, hypoglycemics, opioids and herbals as well as two samples of antiseptics did not comply with specifications. This represents the lowest failure rate of samples analyzed in DARU and presented as pentad reports since the year 1991.

Background: The oral cavity harbors many microbes that may cause diseases, including dental caries and periodontal diseases. Progressive inflammation from periodontal diseases may lead to gum detachment from the teeth. Povidone-iodine and chlorhexidine mouth rinses and gargles are broad-spectrum antimicrobial products that effectively manage dental caries and periodontal diseases and eliminate plaques. This study was conducted in Nairobi County, Kenya to establish the quality of povidone-iodine and chlorhexidine oral care products by determining the content of the active pharmaceutical ingredient and compliance with labeling requirements.
Methods: A total of 34 samples (from 15 brands) of povidone-iodine and 15 samples (from nine brands) of chlorhexidine were collected from retail pharmacies using convenience sampling. All samples were subjected to labeling analysis, identity, and assay tests. Potentiometric titration was used to assay povidone-iodine in the samples, while chlorhexidine was assayed using high-performance liquid chromatography (HPLC) according to British Pharmacopeia 2017 specifications.
Results: All samples complied with identification tests. Moreover, 47.1% of povidone-iodine and 66.7% of chlorhexidine products complied with pharmacopoeial assay specifications. Five povidone-iodine (14.7%) and four chlorhexidine (26.7%) samples had missing label information on the storage conditions and the address of the manufacturer.
Conclusions: Strict adherence to current Good Manufacturing Practices (cGMP) by manufacturers of povidone-iodine and chlorhexidine mouthwashes/gargles is necessary to guarantee quality assured products in the market. Regular post-market surveillance and regulatory enforcement of standards are instrumental in minimizing the circulation of poor-quality products.

The global use of alcohol-based hand sanitizers (ABHS) as an important means of controlling the transmission of infectious disease has increased significantly as governments and public health agencies across the world advocated hand hygiene as a preventative measure during the COVID-19 pandemic. Although the performance of these products is most commonly defined as a function of their alcohol concentration, they are multifaceted products in which an interplay of several factors is important in determining efficacy. This paper discusses the interplay between ABHS input (formulation) factors and output (product performance) factors in the context of a multidimen-sional perspective using a novel representative paradigm. In the model, represented in the form of a three-dimensional tetrahedron, each of the faces represents inputs in the manufacturing of the ABHS product, which are the type and amount of alcohol, the inactive ingredients, the formulation and the manufacturing practices. The four corners of the tetrahedron represent the product per-formance factors which include product efficacy, sensory characteristics, usage and compliance and product safety. The multidimensional approach to the formulation and evaluation of ABHS shows that several factors contribute to the effectiveness and utility of these products. The paradigm provides a useful framework for manufacturers of ABHS and related healthcare products.

A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (1), along with eight known compounds—voacangine (2), voacristine (3), coronaridine (4), tabernanthine (5), ibox-ygaine (6), voacamine (7), voacorine (8) and conoduramine (9)—were isolated from the stem bark of Voacanga africana. The structures of the compounds were determined by comprehensive spec-troscopic analyses. Compounds 1, 2, 3, 4, 6, 7 and 8 were found to inhibit the motility of both the microfilariae (Mf) and adult male worms of Onchocerca ochengi, in a dose-dependent manner, but were only moderately active on the adult female worms upon biochemical assessment at 30 μM drug concentrations. The IC50 values of the isolates are 2.49–5.49 µM for microfilariae and 3.45–17.87 µM for adult males. Homology modeling was used to generate a 3D model of the O. ochengi thioredoxin reductase target and docking simulation, followed by molecular dynamics and binding free energy calculations attempted to offer an explanation of the anti-onchocercal struc-ture–activity relationship (SAR) of the isolated compounds. These alkaloids are new potential leads for the development of antifilarial drugs. The results of this study validate the traditional use of V. africana in the treatment of human onchocerciasis.

Leucas calostachys is widely used in traditional medicine in Kenya for management of various ailments including malaria. Bio-assay guided fractionation of Leucas calostachys extracts was carried out using in-vitro antiplasmodial and β-hematin inhibition assays with semi-preparative high performance liquid chromatography (HPLC). The active methanol fraction was subjected to liquid chromatography tandem mass spectrometry to identify constituent compounds. A total of twenty compounds consisting of eight flavonoids and 12 phenylethanoids were identified from this fraction. The flavonoids included, isorhamnetin, luteolin-7-O-glucoside, luteolin-4′-O-glucoside, luteolin diglucoside, apigenin-O-glucoside, genistein-O-glucoside, chrysoeriol-7-O-glucoside, and chrysoeriol-7-O-glucuronide. Seven of the phenylethanoids were identified as acteoside, isoactoeside, hydroxyacteoside, forthsoside B, samioside, alyssonoside and leucoseptoside A. The antimalarial activity of Leucas calostachys could be linked to presence of flavonoids and phenylethanoids.

Background: Alcohol-based hand sanitizers (ABHS) have become widely used products since the advent of the SARS-CoV-2 coronavirus based COVID-19 pandemic. In addition to ethanol or isopropanol (the active ingredients of ABHS) and water, these products are formulated with a number of ingredients to optimize delivery, efficacy and safety as well as to provide consumer appeal. Despite the widespread use of ABHS, there is very limited information in the literature on the non-alcohol ingredients used in these products.
Objectives: The aim of this work was to determine the inactive ingredients used in ABHS marketed in metropolitan Nairobi.
Methodology: ABHS products were randomly obtained from several locations at retail outlets within the Nairobi metropolitan region. The ingredients used in each ABHS were obtained from the product labels.
Results: The most common inactive ingredients based on percentage frequency of listing on product labels were glycerin (50%), fragrances (36%), carbomer (26%), triethanolamine (18%) and propylene glycol (17%). It was observed that some products incorporated additional antimicrobial agents and preservatives in the formulation. The fragrances and some of the preservatives used in the ABHS products are potential allergens. Incomplete or inadequate ingredient naming was noted for several products.
Conclusions: There is a need for ABHS manufacturers to fully disclose all raw materials used in ABHS products using standardized ingredient nomenclature. ABHS users need to be aware of potential allergens present in respective marketed products.

Universal health coverage (UHC) is an integral part of the United Nations sustainable development goals. The private sector plays a prominent role in achieving UHC, being the primary source of essential medicines for many people. However, many private healthcare facilities in low‐ and middle‐income countries (LMICs) have insu_cient stocks of essential medicines. At the same time, these same facilities carry excessive quantities of certain drugs, leading to obsolescence. This suggests poor inventory control. To propose potential remedies it is vital to fully understand the underlying causes. In semi‐structured interviews with managers of private healthcare facilities in Nairobi, we asked them about their 1) inventory control systems, 2) inventory control skills, 3) time/human resource constraints, 4) budget constraints, 5) motivations for inventory control, and 6) suppliers. Our results suggest that the problems are driven by resource limitations (budget and time/human resources), managerial issues (relating to skills and systems), and market mechanisms that limit overage and underage costs. Unavailability at the supplier level and motivations for inventory control are relatively minor issues. We posit that the key causes are interlinked and stem from wider issues in the market and regulatory environment. Our results challenge prevalent beliefs about medicine supply chains in LMICs and lead to alternative hypotheses. Testing these hypotheses could improve our understanding of inventory management in private healthcare facilities and aid progress in achieving UHC.

During the 2013-2017 period, the MEDS laboratory received and processed 6853 samples. Samples were sourced from Kenya and other sub-Saharan Africa countries. The samples submitted comprised Kenyan manufactured (31.9%) and internationally manufactured products (67.9%) while nine samples were of unknown origin. Analysis was carried out according to compendial and/or in-house specifications. The non-compliance rate was 5.1% consisting of 1.2 % local and 3.8% imports. The top ten drug classes with high failure rates were antimyasthenics (50.0%), antiseptics/disinfectants (24.7%), anthelminthics (22.0%), thyroid/antithyroid drugs (20.0%), nutrient mixtures (18.5%), uricosurics (12.5%), waters (11.6%), mixed anti-infectives (11.1%), hemostatics (10.0%) and nootropics (10.0%). Full compliance was however, recorded with laxatives, antidiarrheals, antihemorrhoidals, prokinetics, antithrombotics, antithrombocytopenia agents, vasopressors, anti-arrhythmic drugs, anti-anginal drugs, disease modifying antirheumatic drugs, antimigraine drugs, vertigolytics, muscle relaxants, bisphosphonates, joint lubricants, hormones, anticholinergics, osmotic diuretics, hypophosphatemics, lubricants, minerals, amino acids/peptides, immunomodulatory agents, choleretics, antidotes, lozenges, ear drops, proteins/glycoproteins, herbal products, X-ray contrast media, vaccines, environmental monitoring, medical devices/equipment and cleaning validation swabs. A total of 23 substandard and falsified medicines devoid of active ingredients were encountered over the five-year period. The results obtained demonstrate the need to strengthen regulatory stringency in order to curb incidences of substandard and falsified medicines.

The emergence of the COVID-19 pandemic has propelled the use of alcohol-based hand sanitizers to the fore as a SARS-CoV-2 control measure. To be effective these products must comply with relevant quality parameters such as alcohol concentration, methanol limits and purity. The current study was designed to determine the quality of alcohol-based hand sanitizer products in the Nairobi metropolitan area. For this purpose, 74 commercially marketed samples were collected and subjected to analysis by gas chromatography. Only three samples (4.1%) complied with the regulatory specifications for alcohol content, methanol limits and pH. Five samples (6.8%) complied with the specification for alcohol content but did not meet methanol or pH limits. A total of 44 (59.5%) samples had methanol levels that exceeded threshold limits. Eleven samples (14.9%) were found with methanol substitution (i.e., methanol, instead of ethanol or isopropanol, was the main alcohol component). The results show that users of alcohol-based hand sanitizers are being exposed to substandard and falsified products which in addition to being non-efficacious pose harm due to unacceptable levels of toxic impurities. Regular, routine post-market surveillance is needed to prevent such products from reaching the market.

Metronidazole benzoate is an ester derivative of metronidazole utilized in the formulation of oral suspensions owing to its palatability. The drug is liable to hydrolytic degradation during shelf life which could lower assay values and increase free metronidazole content. A medicine quality survey study was carried out in Nairobi County whereby 32 metronidazole benzoate samples representing 13 brands were collected from retail pharmacies. The samples were subjected to British Pharmacopoeia specifications for pH, free metronidazole content and assay. From the results obtained, only nine samples (28.1%) passed all the quality tests performed while five (15.6%), seven (21.9%) and 18 (56.3%) did not comply with pH, metronidazole content and assay specifications respectively. The results obtained demonstrate the existence of substandard metronidazole benzoate products in the market. This underscores the need for regular post market surveillance surveys and execution of appropriate regulatory actions.

Chemical investigation of the leaves of Manniophyton fulvum led to the isolation of seven flavonoid glycosides: myricetin-3-O-β-Dd-rhamnoside (1), kaempferol-3-O-β-d-rhamnoside (2), quercetin-3-O-β-d-glucoside (3), quercetin-3-O-β-d-rhamnoside (4), quercetin-3-O-β-d-galactoside (5), rutin (6) and quercetin (7). The structures of the compounds were established by spectroscopic analyses as well as by comparison with published data. Some of the compounds showed strong antioxidant activity which validates the traditional use of the plant. An attempted correlation between the computed HOMO-LUMO energies and the measured antioxidant activities was established. We have also estimated the cardiotoxicity of the compounds by calculating the predicted logarithm of the human Ether-`a-go-go Related Gene (loghERG) using the QikProp program. These purified flavonoids are new potential lead compounds for the development of antioxidant drugs.

A recently published FDA guidance on chewable tablets has addressed the quality attributes of this class of dosage forms. This study evaluated disintegration as a quality attribute for a number of commercially available chewable antacid tablets. Additionally, acid-neutralizing-capacity values were evaluated. A number of the products exhibited prolonged disintegration times—which were far longer than those of conventional immediate-release tablets. The mean disintegration times ranged from 6 to more than 60 min in distilled water and from 9 to over 60 min in 0.1 N HCl. The products with longer disintegration times had higher breaking force and tensile strength values. Despite the range in disintegration times, all products met the criteria for acid-neutralizing capacity. These results indicate a need for patients to be aware of the need to thoroughly chew antacid tablets upon administration. Given these considerations, disintegration testing would be a useful quality control test in evaluating these dosage forms as the implicit assumption by the manufacturer that patients will chew the product sufficiently may not be met in every case.

A simple, sensitive, accurate and precise high performance liquid chromatography (HPLC) method for determination of artemisinin in crude plant material was developed and validated. Optimal separation of artemisinin from matrix components in the plant extracts was achieved using a Waters XTerra® RP18 , 5 m, 250 × 4.6 mm column, maintained at 40 °C, a mobile phase consisting of 0.05 M potassium phosphate buffer, pH 6.0 - acetonitrile (60:40) containing 5 mM hexane sulfonate in isocratic flow. The mobile phase flow rate was 1.0 ml/min while elution was monitored at 216 nm. The method satisfied the International Conference on Harmonization (ICH) validation criteria for linearity, accuracy, precision and sensitivity. The developed method is applicable in routine quality control of Artemisia annua crude extracts.

During the period 2011-2015, the Drug Analysis and Research Unit (DARU) analyzed 1972 drug samples. The samples consisted of 21.5% locally manufactured and 78.2% imported products while the origin of 0.3% of products was indeterminate. Samples were subjected to compendial and/or in-house analytical specifications. The overall non-compliance rate was 4.5% comprising 2.5% local products and 2.0% imports. High failure rates were recorded for uterotonics (37.5%), hemostatics (33%), anthelmintics (17%) and anticancers (10.5%) while ophthalmic, immunomodulatory, musculoskeletal and endocrine drugs all complied with the quality acceptance criteria. Erectile dysfunction drugs, received by the laboratory for the first time, all complied with specifications. The results obtained demonstrate an improvement in the quality of samples submitted to DARU when compared to previous performance.

Alcohol based hand sanitizers are currently recommended for routine use in curbing the spread of the COVID-19 global pandemic. The present survey examined hand sanitizers marketed in Nairobi County with regards to product appearance, packaging, labelling and declared composition. Seventy-six samples were collected from five sites within the Nairobi metropolis - Central Business District, Kibera, Kilimani/Karen, Ngong and Thika. A wide range of non-conformities were observed for the criteria applied. Many samples had incomplete or missing label information, ingredient lists, cautionary warnings, Kenya Bureau of Standards (KEBS) standardization marks and permit numbers. Glycerin, fragrances and carbomers were the most common added ingredients. Poor formulation indicators such as haziness and phase separation were encountered in some products. The median price of the products was KES 250 (USD 2.36) per 100 ml although there was considerable variation in pricing of samples. None of the samples evaluated fully met all the standards for the parameters evaluated. Strict adherence to regulatory standards by producers of hand sanitizers is required to ensure that only compliant products are available on the market.

Effective treatment of malaria relies on the availability of quality medicines while pricing is a major determinant of affordability. In addition, adequate numbers of competent staff of different cadres is essential for a well-functioning health system and effective health service delivery. The aim of the study was to determine the availability and prices of antimalarial medicines as well as staffing levels in healthcare facilities located in Embu County, Kenya. Antimalarials were sampled from 11 public (government owned) facilities, 29 private pharmacies, 5 private-for-profit and 3 not-for-profit mission health facilities in May-June 2014. The majority of public facilities (91%) had artemether-lumefantrine (AL) tablets in stock. Government and mission facilities did not stock second line antimalarials or sulfonamide-pyrimethamine (SP). All public facilities provided antimalarials free-of-charge to patients. Private pharmacies stocked a wider variety of antimalarials. The facilities studied were stocked with recommended antimalarials both in the private and public domains. No oral artemisinin monotherapies were encountered during the study. Only 45% percent of public facilities employed pharmacists. Of the remaining facilities, 27% employed pharmaceutical technologists while in the rest of the facilities pharmaceuticals were in the custody of nurses. Notably, none of the private-for-profit or mission facilities had pharmacists employed in their establishments; one facility employed a pharmaceutical technologist, while the rest were staffed by nurses. The number of private pharmacies superintended by pharmacists and pharmaceutical technologists were 7 (24%) and 22 (76%), respectively.

Medicine prices are a major determinant of access to healthcare. Owing to low availability of medicines in the public health facilities and poor accessibility to these facilities, most low-income residents pay out-of-pocket for health services and transport to the private health facilities. In low-income settlements, high retail prices are likely to push the population further into poverty and ill health. This study assessed the retail pricing, availability, and affordability of medicines in private health facilities in low-income settlements within Nairobi County. Medicine prices and availability data were collected between September and December 2016 at 45 private healthcare facilities in 14 of Nairobi’s low-income settlements using electronic questionnaires. The International Medical Products Price Guide provided international medicine reference prices for comparison. Affordability and availability proxies were calculated according to existing methods. Innovator brands were 13.8 times more expensive than generic brands. The lowest priced generics and innovator brands were, on average, sold at 2.9 and 32.6 times the median international reference prices of corresponding medicines. Assuming a 100% disposable income, it would take 0.03 to 1.33 days’ wages for the lowest paid government employee to pay for treatment courses of selected single generic medicines. Medicine availability in the facilities ranged between 2% and 76% (mean 43%) for indicator medicines. Prices of selected medicines varied within the 14 study regions. Retail medicine prices in the low-income settlements studied were generally higher than corresponding international reference prices. Price variations were observed across different regions although the regions comprise similar socioeconomic populations. These factors are likely to impact negatively on healthcare access.

Background: Quality pharmaceutical services are an integral part of primary healthcare and a key determinant of patient outcomes. The study focuses on pharmaceutical service delivery among private healthcare facilities serving informal settlements within Nairobi County, Kenya and aims at understanding the drug procurement practices, task-shifting and ethical issues associated with drug brand preference, competition and disposal of expired drugs. Methods: Forty-five private facilities comprising of hospitals, nursing homes, health centres, medical centres, clinics and pharmacies were recruited through purposive sampling. Structured electronic questionnaires were administered to 45 respondents working within the study facilities over an 8-week period.
Results: About 50% of personnel carrying out drug procurement belonged to non-pharmaceutical cadres namely; doctors, clinical officers, nurses and pharmacy assistants. Drug brand preferences among healthcare facilities and patients were mainly pegged on perceived quality and price. Unethical business competition practices were recorded, including poor professional demeanour and waiver of consultation fees veiled to undercut colleagues. Government subsidized drugs were sold at 100% profit in fifty percent of the facilities stocking them. In 44% of the facilities, the disposal of expired drugs was not in conformity to existing government regulatory guidelines. Conclusions: There is extensive task-shifting and delegation of pharmaceutical services to non-pharmaceutical cadres and poor observance of ethical guidelines in private facilities. Strict enforcement of regulations is required for optimal practices.

Beverage fraud involving counterfeiting of brand spirits is an increasing problem not only due to deception of the consumer but also because it poses health risks e.g. from possible methanol admixture. Suspicious spirit samples from Russia and Kenya were analysed using 1H nuclear magnetic resonance (NMR) spectroscopy in comparison to authentic products. Using linear regression analysis of spectral integral values, 4 counterfeited samples from Russia and 2 from Kenya were easily identifiable with R2 < 0.7. Sensory analysis using triangle test methodology confirmed significant taste differences between counterfeited and authentic samples but the assessors were unable to correctly identify the counterfeited product in the majority of cases. An important conclusion is that consumers cannot assumed to be self-responsible when consuming counterfeit alcohol because there is no general ability to organoleptically detect counterfeit alcohol. Beverage fraud involving counterfeiting of brand spirits is an increasing problem not only due to deception of the consumer but also because it poses health risks e.g. from possible methanol admixture. Suspicious spirit samples from Russia and Kenya were analysed using 1H nuclear magnetic resonance (NMR) spectroscopy in comparison to authentic products. Using linear regression analysis of spectral integral values, 4 counterfeited samples from Russia and 2 from Kenya were easily identifiable with R2 < 0.7. Sensory analysis using triangle test methodology confirmed significant taste differences between counterfeited and authentic samples but the assessors were unable to correctly identify the counterfeited product in the majority of cases. An important conclusion is that consumers cannot assumed to be self-responsible when consuming counterfeit alcohol because there is no general ability to organoleptically detect counterfeit alcohol.

Background
Common cold is the most common infection of the upper respiratory tract and cold-cough syrups are often prescribed. Although menthol is one of the common constituents of these syrups, quality checks on cold-cough syrups normally target the major active pharmaceutical ingredients without regard to menthol content.

Objective
To develop and validate a gas chromatography method for determination of menthol in cold-cough syrups.

Methods
A simple, rapid, robust, accurate and reliable Gas Chromatography method was developed and validated for the determination of menthol in cold-cough syrups that may also contain ambroxol, chlorpheniramine, guaifenesin, bromhexine and salbutamol.

Results
Optimized chromatographic conditions were: A ZB-WAXplus 60m ×0.25mm; 0.25μm fused silica capillary column. Oven temperature program of 110 0C (2 min), ramp 10 0C/min to 190 0C (2 min). Injector port temperature maintained at 240 0C. Injection volume of 1.0 μl split in the ratio of 50:1. Carrier gas as nitrogen at 1.0mL/min which also serves as make up gas (30 mL/min) in the flame ionization detector (260 0C). Other detector gases were hydrogen (30 mL/ min) and industrial air (300 mL/ min) and the diluent for samples and standards was grade chloroform.
From recovery studies, 97.56 to 102.97 % recovery was reported. Repeatability studies had a coefficient of variation of 0.55 while intermediate precision was 0.32. The method was linear over a range of 0.042 to 0.169 mg/mL with a coefficient of determination (R2) 0.9986.
Of the 21 samples analyzed, only 10 samples (47.6 %) complied with assay specifications of 90.0 to 110.0 % label claim for finished products according to the United States Pharmacopeia 2016.

Conclusion and recommendation
A gas chromatographic method was developed and validated for the determination of menthol in cold-cough syrups in Kenya. This method can be used together with a validated high-performance liquid chromatography method to assay cold-cough syrups that may also contain ambroxol, bromhexine, chlorpheniramine maleate, guaifenesin and salbutamol.
This method can be useful in routine analysis such as pre-registration studies as well as post market surveillance to curb substandard and counterfeit cold-cough syrups.

Background:
Malaria is a major health problem in sub-Saharan Africa where over 90% of the world’s malaria cases occur. Artemisinin-based combination therapy (ACT) is recommended by the World Health Organization as first-line and second-line treatments for uncomplicated falciparum malaria. However, there are a growing number of reports of sub-standard and falsified anti-malarial medicines in sub-Saharan Africa.

Methods:
A cross-sectional study was conducted in Embu County, Kenya on the quality of anti-malarial medicines available in public and private facilities. Sampling of anti-malarial medicines from public and private hospitals, health centers and pharmacies was conducted between May and June 2014. Quality control tests were performed at the Drug Analysis and Research Unit, University of Nairobi, using ultraviolet spectrophotometry and high-performance liquid chromatography. A test for microbial load was also conducted for suspension formulations.

Results:
A total of 39 samples were collected from public and private facilities across the Embu County. A visual inspection of the medicines showed no signs of sub-standard or falsification. All ACT passed identification, assay and dissolution tests. Of 11 suspension samples collected, none failed the microbial load test although one sample had 50 colony forming units (cfu). No oral artemisinin monotherapy medicines were encountered during the survey. Amodiaquine and chloroquine monotherapy products accounted for 5% of the collected samples, despite their ban in Kenya. Two herbal anti-malarial formulations were collected during the survey. Sulfadoxine/pyrimethamine (SP) was also found to be available use for malaria treatment, not in accordance with malaria treatment guidelines.

Conclusion:
All the anti-malarial drugs analysed in this study passed the quality control tests. This is encouraging given the high malaria burden in Kenya. Regulatory actions are required to counter SP and herbal products for malaria treatment.

Samples of unrecorded opaque beers (n=58; 40 based on maize, 5 on sorghum and 13 on other plants) and recorded wines (n=8) in Kenya were screened for aflatoxins using a rapid ELISA technique followed by confirmation using liquid chromatography-tandem mass spectrometry. Six of the maize beers were obtained from Kibera slums in Nairobi County. Aflatoxin contamination was detected in six unrecorded beers (10%), but in none of the recorded wines. Remarkably, three of the aflatoxin positive samples were from the Kibera slums.
The concentration of aflatoxins in the positive samples had a mean of 3.5 µg/L (range 1.8–6.8 µg/L), corresponding for an average consumption of 500 mL (1 standard drink) to a margin of exposure (MOE) of 36 (range: 15–58), which is considered as risk. On the other hand, the alcoholic strength of the aflatoxin positive samples had a mean of 4.3% vol (range 3.5-4.8%) corresponding to a MOE of 2.5 (range of 2.2-3.0) for the equivalent consumption volume. While aflatoxins pose a risk to the consumer, this risk is about 10 times lower than the risk of ethanol.
The Joint FAO/WHO Expert Committee on Food Additives sets no acceptable daily intake for aflatoxins since they are genotoxic carcinogens and instead recommends for the reduction of aflatoxin dietary exposure as an important public health goal, particularly in populations who consume high levels of any potentially aflatoxins contaminated food. Nevertheless, ethanol still posed a considerably higher risk in the unrecorded beers examined. However, consumers should be informed about aflatoxins, as these are an involuntary and unknown risk to them. In addition, producers should be educated about measures to reduce aflatoxins.

The root bark of Lonchocarpus eriocalyx was dried, powdered and extracted using chloroform, methanol and hot water. The extracts exhibited antibacterial activity against Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus and antifungal activity against Saccharomyces cerevisiae. The decoction (100mg/ml) was more active than the chloroform and methanol extracts against the four microorganisms. Chromatographic fractionation of the chloroform extract using normal phase silica yielded the phytosterols lupeol and lupenone. At 100 mg/ml, the compounds were active against all the four microorganisms, with lupeol being more active than lupenone. This is the first report of the isolation of lupenone from Lonchocarpus eriocalyx.

Cheap licit and artisanal illicit spirit drinks have been associated with numerous outbreaks of alcohol poisoning especially with methanol. This study aimed to evaluate the quality of cheap spirit drinks in Kibera slums in Nairobi County, Kenya. The samples consisted of cheap licit spirits (n = 11) and the artisanal spirit drink, ‘chang’aa’, (n = 28). The parameters of alcoholic strength and volatile composition were used as indicators of quality and were determined using gas chromatography with flame ionization detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS) respectively. The ranges for alcoholic strength were 42.8–85.8% vol and 28.3–56.7% vol for chang’aa and licit spirit drinks respectively, while the pH ranges were 3.3–4.2 and 4.4–4.8 for chang’aa and licit spirit drinks respectively. The majority of volatiles were found in artisanal spirits and they included higher alcohols, ethyl esters and carbonyl compounds. The alcoholic strength of all the artisanal spirits (100%) and 91% of the licit spirits was above the 40% vol of standard spirits such as vodka. The high ethanol content of the alcohol products was the only element of public health significance in this study.

A simple, rapid isocratic liquid chromatography method was developed for the simultaneous determination of diphenhydramine, promethazine, chlorpheniramine, and ephedrine in cold-cough syrups commonly available in the Kenyan market. The influence of the percentage of organic modifier, ion pairing agent, buffer concentration as well as pH and column temperature on the selectivity with respect to analytes was investigated. Optimum chromatographic separation was achieved using a C18 Gemini NX column (250 mm × 4.6 mm, 5 μm) maintained at 40°C and a mobile phase comprising methanol –triethylamine-0.2 M ammonium acetate pH 5.0 -water mixture (50:0.15: 40:9.85, v/v) delivered at a flow rate of 1.0 mL/min. Upon validation, the proposed liquid chromatography method satisfied the International Committee on Harmonization acceptance criteria for linearity, sensitivity, precision, and robustness. The method was applied in the analysis of commercial samples obtained from Nairobi County, Kenya. The method can be used in routine analysis of cold-cough syrups containing the specified compounds.

Keywords: diphenhydramine; promethazine; chlorpheniramine; ephedrine, cold-cough syrups.

Clarithromycin is a broad-spectrum semi-synthetic macrolide indicated for treatment of pneumonias, Helicobacter pylori, and chlamydial and skin infections. The object of this study was to evaluate the pharmaceutical equivalence of 14 generic clarithromycin products marketed in Nairobi County, Kenya, to the innovator products, using in vitro dissolution profiles and similarity factors (f2). Further, dissolution profiles of four innovator formulations manufactured in different sites were compared. Fourteen clarithromycin tablets/capsules and four suspensions were subjected to assay and comparative dissolution runs at pH 1.2, 4.5 and 6.8, for 60 and 90 min, respectively. All products complied with pharmacopoeial assay specifications. However, significant differences were observed in their dissolution profiles. The non-compliance rates for tablets/capsules were 50% at pH 1.2, 33% at pH 4.5 and 50% at pH 6.8, while none of the four suspensions were compliant. Overall, only four (25%) products complied with the specifications for similarity factor. The results obtained indicate that a significant percentage of generic clarithromycin products are pharmaceutically non-equivalent to the innovator products, and that assay and single-point dissolution tests are insufficient demonstration of equivalence between the generic and innovator products.

A simple, isocratic and robust RP-HPLC method for the analysis of azithromycin was
developed, validated and applied for the analysis of bulk samples, tablets and suspensions. The
optimum chromatographic conditions for separation were established as a mobile phase comprised
of acetonitrile-0.1 M KH2PO4 pH 6.5-0.1 M tetrabutyl ammonium hydroxide pH 6.5-water (25:15:1:59
v/v/v/v) delivered at a flow rate of 1.0 mL/min. The stationary phase consisted of reverse-phase
XTerra® (250 mm × 4.6 mm i.d., 5 μm particle size) maintained at a temperature of 43 °C with a UV detection at 215 nm. The method was found to be linear in the range 50%–150% (r2 = 0.997). The limits of detection and quantification were found to be 0.02% (20 μg) and 0.078% (78 μg), respectively, with a 100.7% recovery of azithromycin. Degradation products of azithromycin in acidic and oxidative environments at 37 °C were resolved from the active pharmaceutical ingredient and thus the method is fit for the purpose of drug stability confirmation.

Background

Malaria remains a major health problem worldwide especially in sub-Saharan Africa. In Kenya, 80% of the population is at risk of contracting the disease. Pregnant mothers and children under five years are the most affected by this disease. Antimalarial drug resistance poses a major threat in the fight against malaria necessitating continuous search for new antimalarial drugs. Due to inadequate and inaccessible health facilities, majority of people living in rural communities heavily depend on traditional medicine which involves the use of medicinal plants for the management of malaria. Most of these indigenous knowledge is undocumented and risks being lost yet such information could be useful in the search of new antimalarial agents.

Aim of study

An ethnobotanical survey was carried out among the Luhya community of Kakamega East sub-County, a malaria epidemic region, with the aim of documenting the plants used in the management of malaria.

Materials and methods

Semi-structured questionnaires were used to collect information from 21 informants who included traditional medicine practitioners and other caregivers who had experience in use of plants in management of malaria. These were drawn from 4 villages located in Kakamega East sub-county, within Kakamega County based on their differences in topography. Information recorded included plant names, parts used, mode of preparation and administration and the sources of plant materials. A literature search was conducted using PubMed and google scholar to identify the reported traditional uses of these plants and studied antiplasmodial activities.

Results

In this study, 57% of the informants were aged above 50 years and a total of 61% had either no formal education or had only attained primary school education. A total of 42 plant species belonging to 24 families were identified. Most plants used in the management of malaria in this community belonged to Lamiaceae (18%), Leguminosae (9%) and Compositae (9%) plant families. Plants mostly used included Melia azedarach L, Aloe spp, Ajuga integrifolia Buch. Ham, Vernonia amygdalina Del., Rotheca myricoides (Hochst.) Steane and Mabb, Fuerstia africana T.C.E.Fr., Zanthoxylum gilletii (De Wild.) P.G.Waterman and Leucas calostachys Oliv. Rumex steudelii Hochst.ex A. Rich and Phyllanthus sepialis Müll. Arg are reported for the first time in the management of malaria. Although Clerodendrum johnstonii Oliv. ( Jeruto et al., 2011) and Physalis peruviana L.(Ramadan et al., 2015) are reported in other studies for management of malaria, no studies have been carried out to demonstrate their antiplasmodial activity.
The plant parts mostly used were the leaves (36%) and stem barks (26%). Majority of these plants were prepared as decoctions by boiling and allowed to cool before administration (66%) while infusions accounted for 28% of the preparations. The literature mined supports the use of these plants for the management of malaria since most of them have demonstrated in-vitro and in-vivo antiplasmodial activities.

Conclusion

Most of the reported plant species in this study have been investigated for antiplasmodial activity and are in agreement with the ethnomedical use. Two (2) plants are reported for the first time in the management of malaria. There is need for documentation and preservation of the rich ethnomedical knowledge within this community given that most of the practitioners are advanced in age and less educated. There is also the danger of over-exploitation of plant species as most of them are obtained from the wild, mainly Kakamega forest. Therefore, there is need for determining the economically and medicinally important plants in this community and planning for their preservation.

A simple, rapid, isocratic stability indicating reverse phase liquid chromatography method was developed for the assay of rufinamide bulk drug and tablets. The method achieved adequate resolution of rufinamide, related substances A and B as well as laboratory generated degradation products. The method uses a Phenomenex® Hyperclone BDS C-18 column (250 × 4.6 mm, 5 μ) maintained at 35 °C and a mobile phase composed of methanol-0.1 M octane sulfonic acid-0.1 M KH2PO4, pH 6.5-water (30:10:5:55, % v/v/v/v) delivered at a flow rate of 1.0 ml/min. The eluents were monitored by means of ultraviolet detection at 210 nm. During validation, the method satisfied the International Conference on Harmonization acceptance criteria for linearity sensitivity, precision, accuracy, and robustness. The developed method may be applied in the routine analysis of rufinamide bulk material and tablets as well as stability studies.

A simple, rapid, isocratic, and versatile liquid chromatographic method was developed for the simultaneous
determination of bromhexine, guaifenesin, ambroxol, salbutamol/terbutaline, pseudoephedrine, triprolidine, and
chlorpheniramine maleate in cough–cold syrups commonly marketed in Kenya. Separation was achieved using
a Gemini® NX C18 column (250 × 4.6 mm, 5 μm) maintained at 40 °C and a mobile phase consisting of acetonitrile-0.25 M sodium hexanesulphonate-0.2 M ammonium acetate, and pH 3.0-water (35:4:10:51, % v/v/v/v) delivered at 1.0 mL min−1. The eluents were monitored by means of UV detection at 254 nm. During validation, the method satisfied the International Committee on Harmonization acceptance criteria for linearity, sensitivity, precision, accuracy, and robustness. The developed liquid chromatographic method was applied in the analysis of nine commercial samples obtained from Nairobi City County, Kenya. Extraction procedures were not applied during the assay of the samples, thus significantly shortening the analysis time.

A simple, rapid, sensitive, specific, accurate, precise and fast high performance liquid
chromatographic method for the determination of antihypertensive drugs amlodipine,
valsartan and hydrochlorothiazide singly or in combination was developed and
validated. Separation of the analytes was achieved on a Hypersil C-18 (250 mm × 4.6
mm, 5 μm) column using a mobile phase consisting of acetonitrile-KH2PO4 pH 3.0-
water (75:6:19 % v/v/v) delivered at 1 ml/min, UV detection at 229 nm and 40 oC
column temperature. The precision of the method was demonstrated through
repeatability (coefficient of variation = 0.298-0.724) as well as intermediate precision
(coefficient of variation = 0.435-1.412). The detector response was linear over the 25-
150 % range with R2 ≥ 0.99 for each of the three analytes. The limit of detection for
hydrochlorothiazide, valsartan and amlodipine were 10.72, 21.20 and 14.45 ng, while
the limits of quantification were 35.76, 71.23 and 48.16 ng, respectively. The method
showed satisfactory robustness and accuracy with a recovery of 99.7-100.6 %. The
method was applied in the assay of 6 commercial products containing drugs under
study. The results obtained revealed quality problems among the samples analyzed.

The root bark of Teclea trichocarpa exhibited anthelmintic activity against egg hatching and larval development of sheep nematodes (Strongyloides). Three compounds, namely lupeol, melicopicine and 6-methoxytecleanthine were isolated from the dichloromethane-methanol (50:50) extract of the plant. Melicopicine and 6-methoxytecleanthine exhibited mild anthelmintic activity. The present study lends scientific credence to the traditional use of Teclea trichocarpa in the treatment of human helminth infections.

The aerial parts of Nicandra physaloides plant collected from Kenyatta National Hospital grounds were dried and subjected to acid-base extraction and partitioned to obtain alkaloidal and non-alkaloidal extracts. The non-alkaloidal extract yielded three compounds; withanicandrin, β-sitosterol and stigmasterol after column chromatography. Withanicandrin exhibited antifungal activity against Saccharomyces cerevisiae and Candida albicans but lacked antibacterial activity.

During the period 2006-2010, the Drug Analysis and Research Unit analyzed 583 samples. The samples comprised 50.6% local and 49.4% imported products. Samples were subjected to compendial or in-house specifications. The failure rate was 12.2% for local products and 14.2% for imports. Antibacterial products recorded the highest failure rate (21.6%) while anticancers and drugs acting on the gastrointestinal, respiratory and reproductive systems all passed in the tests performed. The failure rate for antiprotozoals, antimalarials, antifungals, anthelminthics and analgesics was 14.3%, 12.5%, 11.8%, 8.9% and 11.5%, respectively.

The structures of the two compounds were elucidated on the basis of their spectral data as friedelin and
epifriedelinol.

During the five-year period January 2001 to December 2005, the Drug Analysis and
Research Unit received and analyzed 394 drug samples. Samples were received from
regulatory authorities, local industry, non-governmental organizations, hospitals
and private practitioners. The samples analyzed constituted 37.8 % locally
manufactured and 62.2 % imported products. In contrast to previous years when
failure rates of over 20 % were recorded, the overall rate of failure to comply with
compendial quality specifications was 6.1 %, comprising of 8.7 % locally
manufactured and 4.5 % imported drugs.

During the period 2000-2003, the Drug Analysis and Research Unit received and analyzed 33 samples of antiretroviral drugs. Locally manufactured products accounted for 57.6% of the samples, while the imported drugs constituted 42.4%. The drugs consisted of single, double and triple component preparations. They were subjected to identity, assay and dissolution tests. 30 samples (90.9%) complied with compendial specifications for these tests, while 3 failed. The results obtained show that the manufacture of quality generic antiretroviral drugs is achievable.

Ajuga remota Benth is the most frequently used plant to treat malaria by Kenyan herbalists. Both crude extracts and pure isolates of the plant were tested for their in vitro antimalarial properties. The activity was assessed by an enzyme assay method based on the measurement of the parasite lactate dehydrogenase activity. The IC50 of the most active A. remota extract (ethanol macerate) was 71 and 69 μg/ml against the chloroquine sensitive (FCA/20GHA) and resistant (W2) strains of Plasmodium falciparum respectively. Ajugarin-1 was moderately active with IC50 of 23.0 ± 3.0 μM as compared to chloroquine (IC50 = 0.041 ± 0.003 μM) against the chloroquine-sensitive strain of Plasmodium falciparum. Ergosterol-5, 8-endoperoxide was about 4x as potent (IC50 = 5.4 ± 1.9 μM) while 8-0- acetylharpagide, a new isolate of A.remota and whose structure was established by spectroscopic evidence, was inactive.

The Drug Analysis and Research Unit received and analyzed 261 drug samples over a five-year period 1996 to 200. Samples were received from regulatory authorities, local industry, non-governmental organizations, hospitals and private practitioners. The samples analyzed constituted 59.8 % locally
manufactured and 40.2 % imported products. The overall rate of failure to comply with
quality specifications set out in the respective monographs was 21.1 %. This represents 24.6%
and 16.2 % of the locally manufactured imported drugs respectively.

Zinc phosphide, a commonly used rat poison in Kenya was mixed with maize flour in a concentration of 0.15% w/w and fed to a group of 60 experimental mice for 3 hours. The mice were then randomly divided into 5 equal groups A, B, C, D and E. To groups A, B, C and D was administered activated charcoal (3% w/v), sodium bicarbonate (10% w/v), hydrogen peroxide(0.5% v/v) and potassium permanganate (1:5000) respectively. Group E was given 1 ml distilled water and used as control. All five groups were observed for symptoms of toxicity, often culminating in death. The observations were continued over a period of 36 hours. Results of the experiment showed that all for test substances minimized the lethal effect of zinc phosphide. Although no attempt was made to quantify the antidotal effect of the 4 substances, activated charcoal appeared to have a higher effect than the others, while potassium permanganate had a low rating.

Clarithromycin is a 6-O-methylated semi-synthetic derivative of erythromycin A,
which is more resistant towards acid decomposition. Commercial clarithromycin
samples contain several potential impurities arising from the manufacturing process
and degradation. A simple, selective, and sensitive isocratic liquid chromatographic
method has been developed for the impurity profiling of clarithromycin bulk samples.
The method employs a XTerra RP18, 5 lm, 25064.6 mm column thermostated at
568C. The mobile phase consists of acetonitrile ± 0.2 M potassium phosphate buffer
pH 6.80 ± water (40 : 3.5 :56.5). Several peaks are of unknown identity. The method
is stability indicating.

This report describes an investigation into the effect of oxamniquine on systemic clearance of theophylline in rat. Male Wister rats (N=12, 5 weeks old) were divide into 3 groups (N=4 per group) and administered buffer plus theophylline (10 mg/kg), controls, oxamniquine( 5 mg/kg), and theophylline (10 mg/kg) oxamniquine (20 mg/kg) intravenously. Theophylline clearance was estimated from a single plasma sample obtained 6 hours post drug administration. Oxamniquine had no effect on theophylline clearance compared to controls. It was concluded that clinically important interaction between oxamniquine and theophylline is unlikely to occur.