Hibiscus sabdariffa aqueous extract (HS) is often used as complementary therapy for hypertension. However, some studies have shown that coadministration with a conventional antihypertensive drug can affect drug potency. We compared the effects of HS plus captopril (CAP) coadministration to HS and CAP administration alone on blood pressure and renin-angiotensin-aldosterone system (RAAS) biomarkers in the rat two-kidney-one-clip (2K1C) model of hypertension. Male Sprague Dawley rats were randomly divided into seven groups (n=6/group), a normal control (SHAM) group, and six 2K1C groups. In 2K1C animals, hypertension was induced using a stainless microclip (inner diameter of 0.20 mm). Four weeks after 2K1C surgery, blood pressure was significantly higher than in the SHAM group. Then, model rats were randomly divided into negative control (2K1C, no treatment), positive control (4.5 mg captopril/200 g body weight [BW] orally [p.o.]), HS alone (30 mg/200 g BW; p.o.), and 3 co-treatment groups receiving HS (15, 30, or 60 mg/200 g BW; p.o.) plus 4.5 mg/200 g BW captopril. The treatments were performed for two weeks. Blood pressure was significantly reduced by all the drug treatments to near the level of SHAM controls. Plasma renin level, serum angiotensin converting enzyme (ACE) activity, and plasma angiotensin II level were also significantly elevated in the 2K1C group compared to the SHAM group. Both serum ACE activity and plasma angiotensin II level were significantly reduced to near SHAM group levels by all the drug treatments. Hibiscus sabdariffa aqueous extract alone can reduce blood pressure. This extract appears could be used as a supplement with captopril but may not provide any additional benefit.

An infectious disease, COVID-19, caused by a new type of coronavirus, has been discovered recently. This disease can cause respiratory distress, fever, and fatigue. It still has no drug and vaccine for treatment and prevention. Therefore, WHO recommends that people should stay at home to reduce disease transmission. Due to the quarantine, FDA stated that this could hamper drug development clinical trial protocols. Hence, an alternative sampling method that can be applied at home is needed. Currently, volumetric absorptive microsampling (VAMS) has become attention in its use in clinical and bioanalytical fields. This paper discusses the advantages and challenges that might be found in the use of VAMS as an alternative sampling tool in clinical trials and therapeutic drug monitoring (TDM) during the COVID-19 pandemic. VAMS allows easy sampling, can be done at home, storage and delivery at room temperature, and the volume taken is small and minimally invasive. VAMS is also able to absorb a fixed volume that can increase the accuracy and precision of analytical methods, and reduce the hematocrit effects (HCT). The use of VAMS is expected to be implemented immediately in clinical trials and TDM during this pandemic considering the benefits it has.

Introduction: Mahanimbine alkaloid is carbazole alkaloids found in kemuning (Murraya paniculata (L.) Jack) potentially as antihyperlipidemia. Chemical compounds from plants can be obtained by extraction. The aim of this study was to determine influence of extraction solvents on the yield, phytochemistry and LCMS profiles from standardized kemuning to produce safe and quality medicinal raw materials. Materials and Methods: The study was used kinds of ethanol concentration with different polarity as a solvent for extraction. Solvent 40%, 70% and 96% of ethanol were used for maceration of simplicia from Bogor, West Java. The extract obtained was evaluated for the content of alkaloid compounds for LCMS then extracts were selected to be proceed to standardized extract quality. Results: The LCMS results showed that all 40%, 70% and 96% ethanol extracts contained Candidate Mass 354,19014 compounds which were thought to be e alkaloids based on the m/z value. Phytochemical screening in all extracts contained alkaloid compounds, flavonoids, saponins, tannins and steroids/triterpenoids. 96% ethanolic extract contained non-specific parameter such as content of compounds soluble in water 22,73%, soluble in ethanol 17,37%, drying down 9,10%, water content 18,36%, total ash content 4,18%, the yield of extracts was 33,45%, microbial contamination <3,0.10 4 (7,0.10 4) colony/g and mold yeast number 0 colony/g. The total gravimetric alkaloid level was 1,031%. Conclusions: 96% ethanolic extract of kemuning contains mahanimbine alkaloids and has met the standard quality requirements of extracts.

Background: The alkylating agent cyclophosphamide is used in chemotherapy regimens for various type of cancer. However, cyclophosphamide may lead to toxic side effects on the bladder, namely hemorrhagic cystitis, which can cause hematuria, and, potentially, bladder cancer. These effects are caused by acrolein, a byproduct of cyclophosphamide metabolism. In this study, a method to quantify 3-hydroxypropyl mercapturic acid (3-HPMA) in urine was developed. 3-HPMA is a stable metabolite of acrolein that serves as biomarker of acrolein. Methods: Urine samples were collected 4 hours after cyclophosphamide administration and analyzed to determine the risk of hematuria. 3-HPMA was analyzed by reverse-phase LC-MS/MS using a triple quadrupole electrospray ionization mass spectrometer in the positive-ion mode. The mobile phase was a 90:10 (vol/vol) mixture of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Multiple reaction monitoring mode was used, with m/z 222.10 → 90.97 for 3-HPMA and 164.10 → 122.02 for the internal standard N-acetyl cysteine (NAC). Samples were prepared by acidification and dilution. Results: The analytical method produced a linear response within the concentration range of 40–10,000 ng/mL. The method was validated in accordance with 2018 FDA guidelines and applied to quantify 3-HPMA in the urine of 40 patients with breast cancer. The measured concentrations ranged from 820.3 to 5596.1 ng/mg creatinine. Seven patients identified with hematuria had low 3-HPMA concentrations of 4445.824 ± 411.17 ng/mg creatinine, and 33 patients without hematuria had low 3-HPMA concentrations of 2419.4 ± 1171.8 ng/mg creatinine. Conclusions: The method was applicable for the quantification of 3-HPMA in human urine. Large variations in 3-HPMA concentrations were found in 40 patients with breast cancer treated with cyclophosphamide, with a significant difference (P < 0.05) observed between patients with hematuria and those without hematuria.

Binahong research, it contains several secondary metabolites of flavonoids, alkaloids, phenols, saponins, triterpenoids and sterols. 7 The methanolic extract of binahong leaves contains 8 glucopyranosyl-4 ', 5,7-trihydroxyprolavones used as blood glucose-lowering agents, 8 and triterpenoid saponin (boussingoside, momordin, ABSTRACT Background: Binahong is a plant that has the potential to be used as a traditional herbal medicine in Indonesia, and has several kinds of classes of compounds, one of them is a flavonoids glycosides (vitexin). Previous research reported that binahong leaves have pharmacological activities as antihyperglycemic, antihyperlipidemic, antibacterial, and others. A traditional plant that has proven efficacious needs to be standardized to ensure the quality and its safety. Objective: This study aimed to characteristics of binahong leaves simplicia obtained from Bogor, West Java. Materials and Methods: The crude extract was obtained by the maceration method using 40%, 70%, and 96% ethanol solvent. The selected extract then standardized, which includes macroscopic and microscopic observations and sets the standard parameter values binahong leaf extract. Parameters LCMS to identify active compounds semiquantitatively. Results: The yield of binahong ethanol extract from 40%, 70%, 96% showed a value of 10.9%, 11.4%, and 12.32%, respectively. From these results, 96% ethanol extract has proceeded for standardization. Macroscopic observation results showed that binahong leaves simplicia has a fine and notched form with 5-10 cm long and 3-7 cm diameter. The microscopic binahong leaves contain palisade tissue, parenchymal tissue, chlorophyll grains, rosette Caoxalate crystals, and spiral type. Phytochemical screening of binahong leaves showed the presence of alkaloids, flavonoids, saponins, tannins, steroids, and phenolic compounds.The standardization of binahong leaves ethanol extract down showed a levels of ethanol-soluble extract> 14.8%, water-soluble extract content > 13.5%, drying < 10%, water content < 8.9%, total ash content < 7.2%. LCMS profiles showed that ethanolic extract 40%, 70%, and 96% all contained vitexin at retention time 5.02 minutes, and m/z values 433.1111. Conclusion: 96% ethanolic extract of binahong leaves contains vitexin with pharmacognostic parameters carried out following the standards listed in the Indonesian herb pharmacopeia. She is expert in the area of Pharmacognosy and Phytochemistry, working in drug discovery of herbal plants, extraction technology, structure elucidation, and degenarative disease such as diabetes mellitus, antyhypertension, and cholesterol.Dwitiyanti, M.Farm., Apt.

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Objective: To develop the method for the simultaneous analysis of cyclophosphamide and 4-hydroxycyclophosphamide (4-OHCP) in Dried Blood Spot (DBS) using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) and its application in breast cancer patients for therapeutic drug monitoring. Methods: Sample preparation used protein precipitation with methanol and acetonitrile (2:1 v/v). The separation was conducted using 1.7μm (2.1 x 100 mm) Waters AcquityTM UPLC C18 column; mobile phase consists of 0.01% formic acid and methanol (50:50 v/v) with isocratic elution, column temperature 30 °C, flow rate 0.3 ml/min and hexamethylphosphoramide (HMP) used as an internal standard. Analysis was performed by a triple quadrupole mass spectrometry with a positive ion mode of Electrospray Ionization. Cyclophosphamide was detected at m/z 260.968>139.978, 4-OHCP at m/z 338.011>224.979, and HMP at m/z 180.17>92.08. The method was applied to quantify cyclophosphamide and 4-OHCP in DBS of breast cancer patients. Blood samples were collected at 2 and 4 h after cyclophosphamide administration for therapeutic drug monitoring. Results: The method was linear in the range of 50–30.000 ng/ml for cyclophosphamide and 10–1000 ng/ml for 4-OHCP. Lower Limit of Quantification (LLOQ) concentration of cyclophosphamide was 50 ng/ml and 4-OHCP was 10 ng/ml. Accuracy and precision within-run and between-run met the requirements with % diff and CV, not exceeding ±15% and not more than ±20% for LLOQ concentration. The results from DBS samples of cancer patients showed that the level of cyclophosphamide was in the range of 6045.980 ng/ml to 37024.403 ng/ml and 4-OHCP was in the range 33.155 ng/ml to 246.362 ng/ml. Conclusion: The developed method met the requirements of all validation parameters under the Guideline on Bioanalytical Method Validation by the European Medicines Agency in 2011. Method can be applied on DBS of cancer patients and the results showed that cyclophosphamide and 4-OHCP was detected on 17 samples of breast cancer patients. This can be one of the parameters for therapeutic drug monitoring.

Objective: This study aimed to analyze doxorubicin and doxorubicinol levels in Dried Blood Spot (DBS) from 25 breast cancer patients who received doxorubicin in their therapeutic regiment. Methods: DBS samples were extracted by protein precipitation method and analyzed using Ultra Performance Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS), with the Acquity UPLC BEH C18 Waters chromatography column (2.1 x 100 mm x 1.7 μm). The mobile phase consisted of 0.1% acetic acid (eluent A) and acetonitrile (eluent B) with gradient elution; the flow rate was 0.15 ml/min and runtime, 7 min. This method was linear within the concentration range of 10–200 ng/ml for doxorubicin and 4–100 ng/ml for doxorubicinol. Result: The analysis results showed that doxorubicin levels were in the range of 11.01 ng/ml to 93.75 ng/ml and doxorubicinol was 5.80 ng/ml to 58.57 ng/ml. Conclusion: Cumulative doses of all patients were in the range of 49.11 mg/m2to 303.70 mg/m2, which have cardiomyopathy incidence rates<4%.