Rapid Capillary Electrophoresis Method for Simultaneous Determination of Abemaciclib, Ribociclib, and Palbociclib in Pharmaceutical Dosage Forms: A Green Approach.

Advances in the treatment of HR+/HER2- breast cancer phenotype have been made with the introduction of abemaciclib, ribociclib, and palbociclib, inhibitors of cyclin D dependent kinases 4 and 6 (CDK4/6). Here, a novel, fast, cheap, and green CE method for the simultaneous determination of these three CDK4/6 inhibitors in less than 4 min is proposed for the first time. Separation was achieved by capillary zone electrophoresis in an acidic medium, in accordance with the structures of the analytes and their pKa values. The optimal pH of the running buffer was found to be 2.9. The optimal method conditions were 27.5 kV separation voltage, 30 °C, 5 s injection time under 50 mbar pressure, and 50 mM phosphate background buffer with benzimidazole as an internal standard. The developed method was validated with respect to robustness, selectivity, accuracy, precision, linearity, and limits of detection. The method was shown to be linear in the range of 10 to 100 µg mL-1 with correlation coefficients higher than 0.9981. A greenness assessment of the proposed method was performed, and the method was shown to be green. The validated method was successfully applied to pharmaceutical dosage forms of all CDK4/6 inhibitors.

Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment.

Palbociclib, ribociclib and abemaciclib were recently approved as chemotherapeutic agents and are currently in the post-marketing surveillance phase. They are used in combination with aromatase inhibitors anastrozole and letrozole or antiestrogen fulvestrant for HR+, HER2- breast cancer treatment. Here, a novel bioanalytical LC-ESI-MS/MS method was developed for the quantitation of these six drugs in human plasma. The samples were prepared by simple protein precipitation followed by solvent evaporation. A Kinetex biphenyl column (150 × 4.6 mm, 2.6 µm) used for chromatographic analysis adequately resolved even the closely eluting aromatase inhibitors' peaks. The mobile phase consisted of 0.1% formic acid in water and in ACN, in a linear gradient. An additional gradient step was added to eliminate the observed carry-over. The proposed method was fully validated in the relevant linear ranges covering the expected plasma concentrations of all six drugs (correlation coefficients between 0.9996 and 0.9931). The intra-day method precision (CV) ranged from 3.1% to 15%, while intra-day accuracy (%bias) was between -1.5% and 15.0%. The inter-day precision ranged from 1.6% to 14.9%, with accuracy between -14.3% and 14.6%, which is in accordance with the EMA and ICH guidelines on bioanalytical method validation. The method was successfully applied to samples from patients treated for HR+, HER2- breast cancer.

Determination of Curcuminoids, Piperine, Boswellic Acids and Andrographolides in Food and Dietary Supplements by HPLC.

Research background: As use of functional food and herbal combination products is ever increasing, methods for quality control of such preparations are necessary. Moreover, low quality of products can cause either lack of benefit or harm to the consumer. In this work, determination of three curcuminoids, piperine, six boswellic acids and three andrographolides, often used in combination products, was carried out in raw materials and dietary supplements. Experimental approach: After extraction optimization using Box-Behnken design, maximum active substance yields were obtained using 81.5% ethanol in hydroethanolic extraction solvent, 30 min sonication time and 60 °C extraction temperature. Afterwards, a high-performance liquid chromatography method was developed and validated, with special attention paid to selectivity, precision and robustness of the method. Lastly, 54 food and dietary supplement samples were analyzed. Results and conclusions: Most products were bought locally, from credible vendors and they all complied with relevant regulatory requirements. However, products obtained on the Internet contained little to no active substances (24% of samples contained less than 20% declared content), presumably showing no efficacy, or were either found to be likely adulterated or contained very high amounts of active substances, compromising safety in terms of dose-dependent adverse effects (one sample containing andrographolides) and pharmacokinetic interactions (one sample containing piperine). In conclusion, consumers should refrain from purchasing such products from the Internet and obtain them only from verified suppliers such as local pharmacies or health stores. Novelty and scientific contribution: This work demonstrates the first developed method for the analysis of aforementioned combination products, which are on the rise today. The method is simple and robust and can be adapted by most laboratories for routine quality control of the said products. Moreover, the work sheds light on the low quality of several products and signifies the need for increased consumer awareness of dangers of taking such products.

A Comprehensive Approach to Compatibility Testing Using Chromatographic, Thermal and Spectroscopic Techniques: Evaluation of Potential for a Monolayer Fixed-Dose Combination of 6-Mercaptopurine and Folic Acid.

In this work, a systematical compatibility investigation of 6-mercaptopurine and folic acid, two commonly used medications in the treatment of inflammatory bowel disease, for the needs of a fixed-dose combination development strategy is shown. Various techniques and approaches, such as differential scanning calorimetry, isothermal stress testing, attenuated total reflectance-Fourier-transform infrared spectroscopy, dissolution medium stability and forced degradation studies, were used to elucidate the possible interactions from different aspects. The results predominantly point to the absence of physicochemical interactions between the examined substances in a variety of possible conditions. However, the forced degradation of the blend of substances and excipients in basic conditions showed a drastic degradation of 6-mercaptopurine, signifying that attention needs to be directed to the careful selection of the excipients for the formulation. To sum up, our findings indicate that a fixed-dose combination of 6-mercaptopurine and folic acid could be produced using one formulation blend, immensely simplifying its manufacture.

Drug-Drug Compatibility Evaluation of Sulfasalazine and Folic Acid for Fixed-Dose Combination Development Using Various Analytical Tools.

The simultaneous administration of sulfasalazine and folic acid is regular practice in the therapy of inflammatory bowel diseases in order to maintain sufficient folate concentration in patients. Having multiple drugs in the therapy increases the possibility of patients failing adherence, thus unintentionally endangering their health. A fixed-dose combination of sulfasalazine and folic would simplify the classical polytherapeutic approach; however, the physicochemical compatibility investigation of two active pharmaceutical ingredients plays an important role in the development of such a product. In this work, various analytical tools were used to determine the physicochemical compatibility of sulfasalazine and folic acid. For the evaluation of chemical compatibility, infrared spectroscopy in combination with advanced statistical methods, such as the principal component analysis and cluster analysis, were used, whilst a simultaneous thermogravimetry/differential thermal analysis gave us an insight into the physical compatibility of two drugs. Isothermal stress testing, forced degradation and dissolution studies, followed by the analysis with a developed chromatographic method for the monitoring of folic acid, sulfasalazine and two of its related impurities, sulfapyridine and salicylic acid, gave us an insight into its chemical compatibility. The combination of the results obtained from the used techniques implies a satisfactory physicochemical compatibility between sulfasalazine and folic acid, which opens the path to the development of the proposed fixed-dose combination.

Development of a HPLC-DAD stability-indicating method and compatibility study of azathioprine and folic acid as a prerequisite for a monolayer fixed-dose combination.

Adherence in chronic diseases is a major problem which can be combated by prescribing fixed-dose combinations in the therapy of the disease. Thus, a combination of azathioprine and folic acid in the treatment of inflammatory bowel disease is highly required, but prior to formulation development, chemical compatibility of the two drugs needs to be investigated. In this work, differential scanning calorimetry, isothermal stress testing, in vitro dissolution and forced degradation studies were utilized to investigate compatibility. Moreover, a stability-indicating HPLC-DAD method for the determination of parent drugs and five of their impurities was developed, validated and applied to the in-house sample. Compatibility testing revealed no noteworthy interactions of the two drug substances. Furthermore, forced degradation showed no substantial differences between the degradation profiles of each active pharmaceutical ingredient, their mixture and the in-house sample, further reinforcing the claim of compatibility. Lastly, the in-house sample was analyzed: it was shown to conform to the requirements of relevant regulatory documents for all the investigated analytes, demonstrating the method's viability for use in formulation and process development. Our results give way to the possibility of realization of said fixed-dose combination.

Fungi and their secondary metabolites in water-damaged indoors after a major flood event in eastern Croatia.

In winter and summer of 2016 and 2017, airborne fungi and house dust were collected in indoors of the village Gunja, which had been flooded, and the control village Gornji Stupnik (Croatia) in order to explore variations of fungal indoor levels, particularly Aspergilli section Nidulantes series Versicolores, as well as fungal metabolites in dust. Levels of airborne Aspergilli (Versicolores) were three times as high in winter and summer in Gunja than in the control village, while dustborne isolates were equally present in both locations. Sequencing of the calmodulin gene region revealed that among Aspergilli (Versicolores), A. jensenii and A. creber were dominant and together with A. puulaauensis, A. tennesseensis and A. venenatus produced sterigmatocystin and 5-methoxysterigmatocystin (HPLC coupled with mass spectrometry); A. amoenus, A. fructus, A. griseoaurantiacus, A. pepii, and A. protuberus produced sterigmatocystin but not 5-methoxysterigmatocystin; A. sydowii did not produce any of these toxins. A total of 75 metabolites related to Penicillium (29), Aspergillus (22), Fusarium (10), Alternaria (5), Stachybotrys (2), and other fungi (7) were detected in dust by liquid chromatography-tandem mass spectrometry. The majority of metabolites including sterigmatocystin and 5-methoxysterigmatocystin exhibited a higher prevalence in winter in Gunja.

A chromatographic approach to development of 5-aminosalicylate/folic acid fixed-dose combinations for treatment of Crohn's disease and ulcerative colitis.

Medication adherence is an important factor in inflammatory bowel disease therapy, which includes regular supplementation of malabsorbed vitamins. Absorption of folic acid is limited due to the damaging of the gastrointestinal tract, which can increase the chances to develop megaloblastic anaemia and colorectal cancer. In this work, 5-aminosalicylates (mesalazine, balsalazide, sulfasalazine and olsalazine) and folic acid were characterized regarding their pharmacokinetic related properties (hydrophobicity, phospholipid and plasma protein binding) using the biomimetic chromatographic approach. Despite the high binding percentage of 5-aminosalicylates for human serum albumin (> 61.44%), results have shown that folic acid binding to human serum albumin protein is far greater (69.40%) compared to α1-acid-glycoprotein (3.45%). Frontal analysis and zonal elution studies were conducted to provide an insight into the binding of folic acid to human serum albumin and potential competition with 5-aminosalicylates. The analytical method for the simultaneous determination of assay in proposed fixed-dose combinations was developed and validated according to ICH Q2 (R1) and FDA method validation guidelines. Separation of all compounds was achieved within 16 min with satisfactory resolution (Rs > 3.67) using the XBridge Phenyl column (150 × 4.6 mm, 3.5 µm). High linearity (r > 0.9997) and precision (RSD < 2.29%) was obtained, whilst all recoveries were within the regulatory defined range by British (100.0 ± 5.0%) and United States Pharmacopeia (100.0 ± 10.0%).

Post-Flood Impacts on Occurrence and Distribution of Mycotoxin-Producing Aspergilli from the Sections Circumdati, Flavi, and Nigri in Indoor Environment.

Mycotoxin-producing Aspergilli (Circumdati, Flavi, and Nigri), usually associated with contaminated food, may also cause respiratory disorders and are insufficiently studied in water-damaged indoor environments. Airborne (N = 71) and dust borne (N = 76) Aspergilli collected at post-flood and control locations in Croatia resulted in eleven different species based on their calmodulin marker: A. ochraceus, A. ostianus, A. pallidofulvus, A. sclerotiorum, and A. westerdijkiae (Circumdati); A. flavus (Flavi); and A. tubingensis, A. welwitschiae, A. niger, A. piperis, and A. uvarum (Nigri). Most of the airborne (73%) and dust borne (54%) isolates were found at post-flood locations, and the highest concentrations measured in indoor air (5720 colony-forming units (CFU)/m3) and dust (2.5 × 105 CFU/g) were up to twenty times higher than in the control locations. A. flavus dominated among airborne isolates (25%) at the unrepaired locations, while 56% of the dust borne Aspergilli were identified as A. tubingensis and A. welwitschiae. The ability of identified isolates to produce mycotoxins aflatoxin B1 (AFB1), fumonisin B2 (FB2), and ochratoxin A were assessed by LC-MS analysis. All ochratoxin A (OTA)-producing Circumdati belonged to A. westerdijkiae (13.7 ± 15.81 µg/mL); in the section, FlaviA. flavus produced AFB1 (2.51 ± 5.31 µg/mL), while A. welwitschiae and A. niger (section Nigri) produced FB2 (6.76 ± 13.51 µg/mL and 11.24 ± 18.30 µg/mL, respectively). Water damage dominantly supported the occurrence of aflatoxigenic A. flavus in indoor environments. Yet unresolved, the causal relationship of exposure to indoor Aspergilli and adverse health effects may support the significance of this research.

Physicochemical Compatibility Investigation of Mesalazine and Folic Acid Using Chromatographic and Thermoanalytical Techniques.

Inflammatory bowel disease is a common name for Crohn's disease and ulcerative colitis. These inflammatory states cause damage in the sidewalls of the gastrointestinal tract, resulting in malabsorption of food and vitamins. Folic acid (Vitamin B9) is often associated with inflammatory bowel diseases since reduced overall folate concentration in the human body may lead to the development of colorectal cancer and megaloblastic anaemia. However, its deficiency is easily compensated by taking an additional folic acid pill during regular therapy. At the moment, there are no studies that have examined the compatibility of folic acid with 5-aminosalicylate drugs used in the treatment of inflammatory bowel diseases. In this work, differential scanning calorimetry, forced degradation studies, isothermal stress testing and dissolution stability testing were used to determine the stability of folic acid and one of the most commonly used 5-aminosalicylates, mesalazine, when present in the same solution or blend. To monitor the assay of folic acid, mesalazine and nine of its related impurities, a single HPLC method was developed. Results of compatibility studies showed that no physicochemical interaction between mesalazine and folic acid occurs when combined, opening the path to the development of new formulations, such as a mesalazine/folic acid fixed-dose combination.

Pharmacokinetic Profiling and Simultaneous Determination of Thiopurine Immunosuppressants and Folic Acid by Chromatographic Methods.

With the increase in the number of medicines patients have to take, there has been a rapid rise of fixed-dose combinations (FDCs) in the last two decades. Prior to FDC development, pharmacokinetic properties of active pharmaceutical ingredients (APIs) have to be evaluated, as well as methods for their determination developed. So as to increase patient compliance in inflammatory bowel disease, three novel FDCs of thiopurine immunosuppressants and folic acid are proposed; physico-chemical and pharmacokinetic properties such as hydrophobicity, lipophilicity and plasma protein binding of all APIs are evaluated. Moreover, experimental results of different properties are compared to those computed by various on-line prediction platforms so as to evaluate the viability of the in silico approach. A simultaneous method for their determination is developed, optimized, validated and applied to commercial tablet formulations. The method has shown to be fast, selective, accurate and precise, showing potential for reliable determination of API content in proposed FDCs during its development.

Lipophilicity and bio-mimetic properties determination of phytoestrogens using ultra-high-performance liquid chromatography.

This paper presents lipophilicity and bio-mimetic property determination of 15 phytoestrogens, namely biochanin A, daidzein, formononetin, genistein, genistein-4,7-dimethylether, prunetin, 3,4,7-trihydroxyisoflavon, 4,6,7-trihydroxyisoflavon, 4,6,7-trimethoxyisoflavon, daidzin, genistin, ononin, sissotrin, coumestrol and coumestrol dimethylether. High-performance liquid chromatography with fast gradient elution and Caco-2 cell line were used to determine the physicochemical properties of selected phytoestrogens. Lipophilicity was determined on octadecyl-sylane stationary phase using pH 2.0 and pH 7.4 buffers. Immobilized artificial membrane chromatography was used for prediction of interaction with biological membranes. Protein binding was measured on human serum albumin and α-1-acid-glycoprotein (AGP) stationary phases. Caco-2 assay was used as a gold standard for assessing in vitro permeability. The obtained results differentiate phytoestrogens according to their structure where aglycones show significantly higher lipophilicity, immobilized artificial membrane partitioning, AGP binding and Caco-2 permeability compared with glucosides. However, human serum albumin binding was very high for all investigated compounds. Furthermore, a good correlation between experimentally obtained chromatographic parameters and in silico prediction was obtained for lipophilicity and human serum albumin binding, while the somewhat greater difference was obtained for AGP binding and Caco-2 permeability.

Green Electroanalytical Method for Fast Measurement of Xanthine Oxidase Inhibitor Febuxostat.

The electrooxidation of xanthine oxidase inhibitor febuxostat was investigated on a boron-doped diamond electrode in aqueous solution. The oxidation of the drug molecule was irreversible and exhibited a diffusion-controlled form. A green electroanalytical method for simple and fast measurements of febuxostat was developed at the unmodified electrode surface. The analyses were performed using square-wave voltammetric peak current at 1.38 V. The linear response was obtained in the range of 7.5 × 10-7 - 2.0 × 10-5 M with the detection limit of 9.5 × 10-8 M. The practical analytical value of the method is demonstrated by quantitative determination of febuxostat in film-coated tablets with excellent recovery of 99.6%. Interference studies reveal that uric acid shows a well-developed voltammetric response at +0.64 V. In view of this, the electroanalytical performances of the boron-doped diamond electrode can open up new possibilities for development of the method for simultaneous clinical analysis of febuxostat and uric acid.

Bismuth nanoparticles-carbon nanotubes modified sensor for sulfasalazine analysis.

Nanocomposite of bismuth nanoparticles and carbon nanotubes in Nafion matrix was used as modifier for glassy carbon electrode in analysis of anti-inflamatory drug sulfasalazine. The nanocomposite surface exhibited exceptional synergy and remarkable enhancement effect to the voltammetric response of drug. The surface morphology and structure characterization of the modified electrodes was characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy and cyclic voltammetry. The sensor exhibited excellent electroanalytical performance for drug determination in comparison with bismuth film electrode. The adsorptive stripping square-wave voltammetric signal showed a good linear correlation to sulfasalazine concentration in a broad range from 5.0×10-8 to 1.0×10-5M with low detection limit of 1.3×10-8M.The method was successfully utilised for drug quantification in human serum samples and good recoveries were obtained without interference from endogenous substances, 5-aminosalycilic acid and sulfapyridine formed after biotransformation of drug and folic acid co-administered as the supplement during sulfasalazine therapy. Additionally, the proposed sensor was successfully applied to analysis of sulfasalazine content in gastro-resistant pharmaceutical dosage forms.

Evaluation of alcohol content and metal impurities in liquid dietary supplements by sHSS-GC-FID and GFAAS techniques.

Despite efforts by many dietary supplements' manufactures to reduce or replace ethanol, many products containing ethanol in concentrations up to 70% are available on market. Furthermore, botanical dietary supplements can vary in metal content as a function of the environment, processing equipment and product containers. Therefore, the aim of study was to develop a new rapid and highly sensitive method for simultaneous determination of ethanol and its impurities in dietary supplements by sHSS-GC-FID technique. In addition, contamination with metals by GFAAS technique was evaluated. The proposed sHSS-GC-FID method was successfully applied for analysis of 93 samples containing various amounts of ethanol. It should be highlighted that the dramatic variation from manufacture's claims was found in even one third of products. Furthermore, high amounts of ethanol were found in several products especially designed for children and in one product labeled as "alcohol-free". Metal impurities were below the limits established by USP.

Electrochemical sensing of mesalazine and its N-acetylated metabolite in biological samples using functionalized carbon nanotubes.

A rapid analytical method without the time-consuming separation step was developed to simultaneously determine mesalazine and its N-acetylated metabolite. A simply designed electrochemical sensor with functionalized carbon nanotubes in a Nafion matrix was constructed for this purpose. The presence of the nanocomposite modifier on the electrode surface significantly affects the voltammetric response of target analytes. The morphology of the modified surface was investigated by scanning electron microscopy. The effect of modifier amount on the sensor performance was investigated in order to obtain the most favorable response of mesalazine since it was found in lower concentration limits in real samples then its metabolite due to the rapid drug elimination and the slightly slower renal metabolite excretion. Under optimal conditions, the anodic peak currents measured by square-wave voltammetry increased linearly after short accumulation of 30s in the range of 5.0×10(-8)-2.5×10(-6)M and 1.0×10(-7)-5.0×10(-6)M for drug and metabolite, respectively. In addition to stable response, the sensor has excellent performance associated with high sensitivity (2.33×10(7) and 8.37×10(6)µAM(-1) for drug and metabolite, respectively). The synergistic effect of the carbon nanotubes and Nafion polymer film yielded detection limit of 1.2×10(-8)M for mesalazine and 2.6×10(-8)M for its metabolite that is comparable to known chromatographic methods. Due to the easy preparation and regeneration, the proposed sensor opens new opportunity for fast, simple and sensitive analysis of drug and its metabolite in human serum samples as well as direct quantification of mesalazine in delayed-release formulations.

Rapid Electroanalytical Method for Determination of Nebivolol at a Boron-Doped Diamond Electrode.

A boron-doped diamond electrode provided a sensitive and cost-effective sensing platform for detection and quantitative determination of novel beta(1)-adrenergic receptor antagonist nebivolol. The net square-wave voltammetric response at 1.31 V related to the oxidation of nebivolol was obtained in Britton-Robinson buffer solution at pH 8. It increased linearly with the drug concentration in the range of 2.5×10(-7) to 1.5×10(-5) M. The LOD attained was 3.2×10(-8) M. The practical analytical approach was illustrated by high speed quantification of nebivolol in a commercial pharmaceutical formulation. The RP-HPLC was selected as a comparative method for evaluating the proposed electroanalytical method. The newly developed method at the unmodified electrode surface was faster and simpler in comparison with HPLC (the retention time was 17.6 min), and only 6 s was necessary for direct voltammetric measurement in the potential range from 0.5 to 1.7 V with a 2 mV potential step and pulse frequency of 100 Hz.

Multi-walled carbon nanotubes/Nafion composite film modified electrode as a sensor for simultaneous determination of ondansetron and morphine.

The electrochemical behavior of ondansetron was studied on the multi-walled carbon nanotubes/Nafion polymer composite modified glassy carbon electrode (MWCNTs-Nafion/GCE). The oxidation peak potential was shifted from 1.32 V to 1.18 V compared to the bare electrode indicating excellent electrocatalytic activity of immobilized film toward drug molecule. The modified electrode exhibited a remarkable enhancement effect on voltammetric response due to the synergistic effect of nanomaterial and cation-exchange polymer on the electron transfer rate, the effective electrode area and the accumulation capability. After optimizing the experimental parameters, adsorptive stripping procedure was used for the determination of ondansetron in pharmaceutical formulation. The results were satisfactory in comparison with those obtained by high-performance liquid chromatography. In addition, the MWCNTs-Nafion/GCE exhibited high selectivity in the voltammetric measurements of ondansetron and co-administrated drug morphine with potential difference of 430 mV. The response peak currents had linear relationship with drug concentration in the range of 1.0 × 10(-7)-5.0 × 10(-6)M and 1.0 × 10(-7)-4.0 × 10(-6)M with detection limits 3.1 × 10(-8) and 3.2 × 10(-8)M for ondansetron and morphine, respectively. The electrode was successfully applied for simultaneous electrochemical sensing of both drugs in human serum samples after selective accumulation at the electrode surface.

Development of a rapid LC/DAD/FLD/MS(n) method for the simultaneous determination of monacolins and citrinin in red fermented rice products.

Red fermented rice is used worldwide by many patients as an alternative therapy for hyperlipidemia; however, the discovery of a toxic fermentation byproduct, citrinin, causes much controversy about the safety of red mold rice products. A new and fast high-performance liquid chromatography method was developed and validated for simultaneous determination of cholesterol-lowering compounds monacolin K (lovastatin), monacolin K hydroxy acid, and other monacolins present in red fermented rice as well as nephrotoxic mycotoxin citrinin in a single run using connected diode array and fluorescence and mass spectrometric detectors. The proposed method was successfully applied for the analysis of red fermented rice food samples and various dietary supplements also containing other natural lipid-lowering agents. The deviations between label content and levels of active compounds found in investigated samples as well as high batch-to-batch variation found in one product indicate that the regular quality control of red fermented rice products is of great importance.

Simultaneous determination of lovastatin and citrinin in red yeast rice supplements by micellar electrokinetic capillary chromatography.

Lovastatin is a main component of Monascus purpureus fermented red rice contributing to the lipid-lowering effect. Citrinin is a toxic fermentation by-product which can be found as a contaminant. An accurate, simple and rapid micellar electrokinetic capillary chromatographic method was developed for the first time for simultaneous determination of lovastatin present in lactone and hydroxy acid forms and citrinin in red rice products provided by different manufacturers and formulated in various dosage forms. Separation was achieved within only 2 min using 20 mM of phosphate buffer at pH 7.0 and 30 mM of sodium dodecyl sulphate at an applied voltage of 25 kV. Sensitivity crucial for detecting citrinin was enhanced by using an extended light path capillary. The results showed that the content of lovastatin and its acid form in dietary supplements were considerably different indicating the need for improved standardization in order to ensure efficiency and safety of these products.