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Clozapine (CLZ) has retained its clinical utility in the management of schizophrenia despite the discovery of novel antipsychotics, as it possesses unique efficacy in the setting of treatment resistant schizophrenia while causing minimal extrapyramidal symptoms. However, these benefits are offset by the risk of agranulocytosis and other side effects, and therapeutic drug monitoring (TDM) is routinely recommended for patients undergoing treatment with CLZ. A multitude of approaches for the quantification of CLZ have been developed for different settings such as TDM, quality control of pharmaceutical dosage forms, and toxicology studies. Primarily, these approaches fall under one of three branches of analysis, namely, chromatography, electrochemical analysis, and spectrophotometry. This study provides a scoping review of the recent advances in the methods of quantification for CLZ and highlights the potential utility of novel methods in the field of drug quantification.

Cassia alata, a traditional herb with a global presence, is renowned for its anti-inflammatory, antibacterial, and antifungal properties, making it a go-to remedy for skin ailments. While it has demonstrated wound healing capabilities in both in vitro and in vivo studies, the precise mechanisms remain elusive. This review aims to highlight its key phytochemicals, their effects, and the mechanism of action. The compounds that have been reviewed and discussed include kaempferol, apigenin, quercetin, rhein, and rutin. These polyphenols play important roles in normal and impaired wound healing processes, encompassing hemostasis, inflammation, proliferation, and tissue remodeling. [ABSTRACT FROM AUTHOR]

To develop and validate HPLC and UV-visible spectroscopy methods for the determination of Thymoquinone (TMQ) content in different solvent extracts of N. sativa L. seed. The evaluation of the free radical scavenging effect of different solvent extracts of TMQ was investigated. Extraction of solvent was done by adding 20 mL of the solvent (hexane, methanol, ethanol, ethyl acetate, and water) to 1 g of blackseed and in a conical flask, respectively. The mixtures were then incubated in a water bath at 40°C for 2 and 4 h, respectively. The mixtures were then centrifuged at 4000 rpm for 10 min at 4°C. The extracts were then quantitatively analyzed using HPLC and UV-visible spectrophotometry. The free radical scavenging activity of TMQ extracts was studied using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The results obtained from HPLC indicate that TMQ extracted using hexane at 4 h (0.075 mg/mL, P <0.05) was significantly higher compared to other extraction solvents used. The results obtained from UV-vis spectroscopy analysis indicate that the methanol extract at 4 h (0.00957 mg/mL, P <0.05) was significantly higher compared to other extraction solvents used. Methanol extracts at 2 h showed the highest free radical scavenging activity (95.8%) compared to other extraction solvents. The results obtained show that hexane extracted the most TMQ at 4 h. Methanol extract demonstrated the highest free radical scavenging activity. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the effects of different extraction methods on the content of thymoquinone using UV-Vis spectroscopy and the antioxidant activities of thymoquinone by measuring the free radical scavenging activity. One gram of powdered Nigella sativa L. black seed was added to 20 mL of solvents (hexane and methanol) into a conical flask and mixed. The mixtures were extracted by different methods which were maceration, percolation, and ultrasonic-assisted extraction. In the percolation method, the mixtures were placed in a water bath of 40°C for 4 h whereas, for maceration, the mixtures were left at room temperature for 4 h. On the other hand, the mixtures were replaced in an ultrasonic bath at room temperature for 2 h in ultrasonic-assisted extraction. The extracts were centrifuged at 4000 rpm at 4°C for 10 min and filtered. The extracts were then analyzed qualitatively and quantitatively by a validated method (UV-Vis spectroscopy). On the other hand, the antioxidant activity was measured by DPPH radical scavenging. In UV analysis, the percolation method with methanol extracted the most content (0.9102%) of thymoquinone. The free radical scavenging activity was observed highest (95.6891%) in the methanol extracts by percolation method. The results in the present study show that methanol extract by percolation method is the best method to extract the main bioactive component, thymoquinone from N. sativa seed. Furthermore, the N. sativa seed extracts exhibit antioxidant activity. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is an inflamed skin condition with relapsing pruritus and cutaneous physiological dysfunction. This skin disorder is widespread around the world and frequently affects infants, children and adults. Natural products with bioactive lead compounds are the source of natural medicines for complementary and alternative therapy in managing AD. Cassia alata has been used traditionally as a remedy for a variety of health issues. In Asian countries, it is used as an ethnomedicine to treat skin conditions such pityriasis versicolor, ringworm, scabies, shingles, urticaria and itching. According to previously published studies, the phytochemicals in C. alata may have a wide range of significant pharmacological effects. AD management is highlighted here, as this review explores the literature on the pharmacological effects of C. alata and its phytochemical content. Specifically, antibacterial, wound healing, anti-inflammatory and antioxidant effects are reviewed and discussed in relation to AD management. [ABSTRACT FROM AUTHOR]

Background: Flibanserin had been approved as the first drug by United State Food and Drug Administration (USFDA) for the treatment of female sexual interest/arousal disorder of any severity. However, the stability of this drug has yet to be studied extensively. Objectives: The objectives of this study were to optimize the stability indicating method and evaluate the stability of flibanserin under various forced degradation conditions, determine the order of the degradation kinetics, half-life and shelf life of flibanserin under certain stress conditions. The stability of flibanserin under various stress conditions which would reflect the important aspects of storage condition and excipients which should be avoided in the formulation of this drug substance into final drug products. Methods: Stability indicating method was developed using HPLC. It was validated according to ICH guideline for its linearity, precision, accuracy, robustness, LOD and LOQ. The forced degradation was performed under various stress conditions, namely acidic, alkaline and oxidative conditions (H2O2, AIBN and FeCl3). LC-MS was utilised for identification of the degradation impurities, and the degradation kinetics was evaluated based on the kinetic models. Results: Degradation of flibanserin was noticed under oxidative conditions. Flibanserin was degraded under H2O2 oxidation at room temperature, while AIBN and FeCl3 at elevated temperature. Two N-oxide impurities were identified under H2O2 oxidation. Flibanserin was degraded following the first-order kinetic under H2O2 and AIBN oxidation, while zero-order under FeCl3 oxidation. Half-life and shelf life of flibanserin under respective stress conditions were determined. Conclusion: It is concluded that the RP-HPLC method developed could be used as the stability indicating method in determination of flibanserin stability and its impurities. Flibanserin is sensitive towards oxidative degradation. The impurities and the order of the degradation kinetics were identified. [ABSTRACT FROM AUTHOR]

Background: Clinacanthus nutans Lindau (family: Acanthaceae), also known as "Sabah Snake Grass" or "Belalai Gajah" in Malaysia, has been widely used by Malaysians due to its anticancer property. However, the anticancer activity of C. nutans leaves extract and its safe use need to be further investigated. The objectives of the present study were to evaluate the cytotoxic effects of methanol leaves extract of C. nutans in various human cancer cell lines and to evaluate the in vitro effect of C. nutans leaves on the activity of CYP3A4 and CYP2E1 in human liver microsomes. Methods: The cytotoxic effects of methanol extract of C. nutans leaves in various cancer cell lines (Hep-G2, A549, HT-29, MDA-MB-231, MCF-7, and CRL 1739) and normal cells (3T3) were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay. The activities of CYP3A4 and CYP2E1 were determined using simple spectrophotometric methods. Results: Results obtained showed that the methanol extract of C. nutans leaves exhibited the highest cytotoxic effect against Hep-G2 cell lines (liver cancer) (IC50 = 13.33 µg/mL), followed by breast cancer oestrogen negative (MDA-MB-231) (IC50 of 18.67 #956;g/mL). Methanol leaves extract of C. nutans showed significant inhibition (p < 0.05) in CYP3A4 and CYP2E1 activity in human liver microsomes. Conclusions: In conclusion, methanol leaves extract of C. nutans exhibited the highest cytotoxic activity against liver cancer cells (Hep-G2). There is a possibility that herb-drug interaction could occur with C. nutans through inhibitory effects on CYP3A4. Additionally, inhibition of C. nutans on CYP2E1 could show anti-carcinogenesis effects in human liver microsomes. [ABSTRACT FROM AUTHOR]

The study aims to develop and validate HPLC and UV-visible spectroscopy methods for the determination of Thymoquinone (TMQ) content in different solvent extracts of N.sativa L. seed. Evaluation of free radical scavenging effect of different solvent extracts of TMQ was investigated. Extraction of solvent was done by adding 20 ml of the following solvent (hexane, methanol, ethanol, ethyl acetate and water) to one gram of blackseed and in a conical flask, respectively. The mixtures were then incubated on a water bath at 40 oC for 2 and 4 hours, respectively. The mixtures were then centrifuged at 4000 rpm for 10 minutes at 4 oC. The extracts were then quantitatively analyzed using HPLC and UV-visible spectrophotometry. The free radical scavenging activity of TMQ extracts was studied using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The results obtained from HPLC indicate that TMQ extracted using hexane at 4 hours (0.075 mg/ml, p < 0.05) was significantly higher compared to other extraction solvents used. The results obtained from UV-vis spectroscopy analysis indicate that the methanol extract at 4 hours (0.00957 mg/ml, p < 0.05) was significantly higher compared to other extraction solvents used. Methanol extracts at 2 hours showed the highest free radical scavenging activity (95.8 %) compared to other extraction solvents. The results obtained show that hexane extracted the most TMQ at 4 hours. Methanol extract demonstrated the highest free radical scavenging activity. [ABSTRACT FROM AUTHOR]

Attenuated total reflectance Fourier transform infrared spectrometric method for determination of crocin in commercial saffron samples was studied. Calibration models were built based on the peaks at spectral region of 1700–900 cm−1and spectral wavenumbers with correlation coefficient (r) greater than 0.99 were selected for quantification of crocin in the samples. The quantitative analysis of samples by attenuated total reflectance Fourier transform infrared was tested against reference UV-visible spectrophotometry method. Considerable correlation (r = 0.95) between both methods in prediction of crocin content among the saffron samples indicated that the proposed methodology has the potential application as a rapid screening tool. [ABSTRACT FROM AUTHOR]

Nigella sativa L., commonly known as black seed, grows natively in the Mediterranean region and Western Asian countries. Nigella sativa L. seeds extracts have diverse medicinal properties. The main active constituent, thymoquinone is medicinally very effective against various health-related issues. The objective of this study was to investigate the effects of different extraction methods and solvents on the content of thymoquinone using HPLC. One gram each of powdered black seed was extracted with 20 mL of hexane, ethyl acetate, methanol, ethanol, and water. The mixture was incubated at 4°C in water bath for 2 hours and 4 hours, respectively. The extraction was repeated for hexane and methanol by maceration, percolation, and ultrasonic assisted extraction (UAE). The extracts were centrifuge at 4000 rpm at 4°C for 10 min and filtered. The extracts were then top-up to 20 mL with the respective solvent and analyzed by HPLC. The results in the present study showed that hexane extract by maceration method is the best method to extract the main bioactive component, thymoquinone from N. sativa L. seed. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of different extraction methods on the content of thymoquinone using HPLC and UV-Vis spectroscopy. To investigate the antioxidant activities of thymoquinone by measuring the free radical scavenging activity. To identify the functional groups of thymoquinone using FTIR analysis. One gram of powdered black seed was added to 20 mL of solvents (hexane and methanol) into a conical flask and mixed. The mixtures were extracted by different methods which were maceration, percolation, and ultrasonic-assisted extraction. In the percolation method, the mixtures were placed in a water bath of 40 °C for 4 hours whereas, for maceration, the mixtures were left at room temperature for 4 hours. On the other hand, the mixtures were placed in an ultrasonic bath at room temperature for 2 hours in ultrasonic-assisted extraction. The extracts were centrifuged at 4000 rpm at 4 °C for 10 minutes and filtered. The extracts were then analyzed qualitatively and quantitatively by a validated method which was HPLC and UV-Vis spectroscopy. The standard thymoquinone was scanned to identify the functional groups present in the chemical structure. On the other hand, the antioxidant activity was measured by DPPH radical scavenging. In HPLC analysis, the maceration method with hexane extracted the most content (1.5299mg) of thymoquinone. On the other hand, in the UV method, the percolation method with methanol extracted the most content (9.1019mg) of thymoquinone. The free radical scavenging activity was observed highest (95.6891%) in methanol extracts from the percolation method. The results in the present study show that hexane extract from the maceration method is the best method to extract the main bioactive component, thymoquinone from N. sativa L. seed. Furthermore, the N. sativa seed extracts exhibit antioxidant activity. [ABSTRACT FROM AUTHOR]

Hypertension is one of the most prevalent non-communicable diseases in the Malaysian population. In addition, it is associated with various mood and psychiatric disorders such as schizophrenia. Recent studies have shown that hypertension leads to worse clinical outcomes in psychiatric patients. Diverse psychosocial factors caused by schizophrenia also impact hypertension and its clinical care. Clozapine and amlodipine are the hallmark drugs for the treatment of schizophrenia and hypertension, respectively. To date, there is no analytical assay that can simultaneously determine the concentrations of these two drugs in human matrices. An Aquasil C18 column was used in the analysis, with the mobile phase consisting of acetonitrile:water (40:60 v/v) adjusted to pH 4.5 with phosphate buffer. Detection with UV spectrometer was done at 240nm. The method was validated according to the International Council for Harmonization (ICH) guidelines. The calibration curves of clozapine and amlodipine were linear in the range of 100-600 ng/mL and 2-12 ng/mL, respectively (r2>0.99). Clozapine limit of detection (LOD) and limit of quantification (LOQ) were 129.5 ng/mL and 392.4 ng/mL, respectively. Meanwhile, amlodipine achieved LOD of 0.25 ng/mL, and LOQ of 0.75 ng/mL. Overall, the study describes quick, precise and sensitive HPLC-UV method for the simultaneous determination of clozapine and amlodipine in human plasma. [ABSTRACT FROM AUTHOR]

Abstract: Aims of the study: Gynura procumbens (Merr.), which is known as “Sambung nyawa”, is widely used in South East Asian countries in the traditional treatment of many ailments. However, there is little toxicological information available regarding safety following repeated exposure. The present investigation describes the toxicity of a methanol extract of Gynura procumbens leaves in rats. Materials and methods: For acute toxicity studies, a methanol extract of Gynura procumbens was orally administered to Sprague–Dawley rats (female and male) at a dose range of 1000–5000mg/kg. For sub-chronic toxicity studies, the rats were orally administered the methanol extract of Gynura procumbens at the doses of 125, 250, and 500mg/(kgday) for a period of 13 weeks. The animals were sacrificed, followed by examination of their organs and blood serum. Results and conclusions: Administration of the methanol extract from Gynura procumbens leaves at 1000–5000mg/kg did not produce mortality or significant changes in the general behaviour, body weight, or organ gross appearance of rats. There were no significant differences in the general condition, growth, organ weights, haematological parameters, clinical chemistry values, or gross and microscopic appearance of the organs from the treatment groups as compared to the control group. Therefore, the NOAEL for the Gynura procumbens methanol extract is 500mg/(kgday) administered orally for 13 weeks. [Copyright &y& Elsevier]

Objectives: Vernonia amygdalina Del. leaves are used in traditional Southeast Asia and Africa medicinal practices. Metformin is used for diabetes management. This study investigated the effect of a single dose of aqueous leaf extract of V. amygdalina on metformin pharmacokinetics in diabetic rats., Methods: Diabetic rats were randomly assigned to four groups, with six rats in each group. Group 1 was administered distilled water. Group 2 was administered V. amygdalina aqueous leaf extract alone. Group 3 was administered metformin alone. Group 4 was co-administered V. amygdalina extract plus metformin. Blood was collected at predetermined intervals, and plasma metformin levels were measured with liquid chromatography. The area under the curve (AUC 0-t ), maximum plasma concentration (C max ), time to reach C max (T max ), half-life (t 1/2 ), and clearance (CL), were calculated based on noncompartment analysis. The effect of the extract on CYP2C9, CYP3A4, and UGT activities was determined using a Fluorometric Screening Kit., Results: The combined treatment altered the pharmacokinetic parameters of metformin. The T max increased from 90±0.18 min to 180±0.13 min and the C max, increased from 0.91±0.32 μg/mL to 2.153±0.28 μg/mL. Additionally, the AUC (0-t) increased from 118.25±1.37 μg min mL -1 to 301.006±1.96 μg min mL -1 and the t 1/2 increased from 34.69±0.61 min to 101.321±0.55 min. However, the CL rate was decreased. The extract inhibited CYP3A4 and CYP2C9 enzyme activities., Conclusions: The alteration of pharmacokinetic parameters by the extract suggests potential herb-drug interactions., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Objectives: Vernonia amygdalina Del. is a perennial tropical shrub from Asteraceae. The fresh leaf of V. amygdalina is consumed as a vegetable due to its medicinal and nutritional properties. The present study focused on the quantification of bioactive compounds, luteolin-7-O-glucoside, luteolin-7-O-glucuronide, and 1,5-O-dicaffeoylquinic acid from aqueous leaf extract of V. amygdalina. The study also aims to investigate the effects of the aqueous leaf extract of V. amygdalina on cytochrome P450 2C9 (CYP2C9), and cytochrome P450 3A4 (CYP3A4) in hepatic cells of control and diabetic rats., Methods: The quantification of the bioactive compounds was conducted using ultra-high-performance liquid chromatography multiple reactions monitoring tandem mass spectrometry (UHPLC-MS/MS-MRM) technique. The effect of the extract on CYP2C9 and CYP3A4 activities was determined using a fluorometric screening kit according to the manufacturer's instructions., Results: The three bioactive compounds were detected and quantified in the aqueous leaf extract. Results showed that the content of luteolin-7-O-glucuronide (47 μg/mg) was the highest followed by luteolin-7-O-glucoside (3.5 μg/mg) and 1,5-O-dicaffeoylquinic acid (1.07 μg/mg). The extract showed an inhibitory effect on CYP3A4 and CYP2C9 enzyme activities in control and diabetic rats., Conclusions: The UHPLC-MS/MS-MRM method is sensitive and reliable for the quality control of V. amygdalina leaf extract. The inhibitory effect of the extract suggests that concomitant use of V. amygdalina leaf preparations with conventional drugs metabolized and eliminated from the body by CYP3A4 and CYP2C9 enzymes may lead to possible interaction., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)