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"Cacao bean Processing into its products may affect catechin and epicatechin contents in the final products. Temperature treatments during cacao processing can induce epimerization reaction of (-)-epicatechin to be (-)-catechin. The aims of this study were : (1) to obtain the valid analytical method which can be used to analyze catechin and epicatechin in cacao bean and cacao products by liquid chromatography mass spectrometry, and (2) to know the influence of temperature during Processing of cacao beans, especially concentration of catechin and epicatechin.Experiment was conducted in three steps, i.e.: optimization of analytical method, validation of selected method, and studying the influence of temperature to catechin and epicatechin concentration during cacao bean processing. Optimization of analytical method was carried out by varying solvents (acetonitrile and methanol) composition using gradient elution. Mobile phase flow rate was set at 0.5, 0.6, 0.8, and 1.0 ml/min. Catechin and epicatechin in cacao samples was detected by mass spectrometry. Condition of mass spectrometer was run by varying ESI voltage, nebulizer pressure, desolvation temperature, and desolvation gas. Validations test included some parameters such as specificity/ selectivity, linearity of calibration curve, limit of detection and limit of quantitation, precision and recovery test. Samples taken during the process were cacao nib, cacao mass, cacao powder and cacao butter.The results of this study showed that analytical conditions for catechin and epicatechin were using mobile phase A (0.1 % formic acid in deionized water) and mobile phase B (acetonitril-methanol - 50:50) at flow rate of 0.5 ml/min. Gradient elution were set at 0 minutes (10% B), 15 minutes (35% B), 20 minutes (40% B), 30 minutes (50% B), 35 minutes (60% B), and 35.1 minute (10% B). Mass spectrometer was set at ESI voltage (-) 3500 volt, desolvation temperature 300 °C, nebulizer pressure 50 psi, desolvation gas 10 L/min, and fragmentor voltage (-) 160 volt. Limit of detection and limit of quantitation of catechin were 0.28 and 0.93 ppm, respectively, while epicatechin were 7.15 and 23.84 ppm, respectively. Based on concentrations of catechin and epicatechin, heat treatment during cacao mass Processing showed a decrease tendency of catechin and epicatechin ratios."

"Cacao bean Processing into its products may affect catechin and epicatechin contents in the final products. Temperature treatments during cacao processing can induce epimerization reaction of (-)-epicatechin to be (-)-catechin. The aims of this study were : (1) to obtain the valid analytical method which can be used to analyze catechin and epicatechin in cacao bean and cacao products by liquid chromatography mass spectrometry, and (2) to know the influence of temperature during Processing of cacao beans, especially concentration of catechin and epicatechin.Experiment was conducted in three steps, i.e.: optimization of analytical method, validation of selected method, and studying the influence of temperature to catechin and epicatechin concentration during cacao bean processing. Optimization of analytical method was carried out by varying solvents (acetonitrile and methanol) composition using gradient elution. Mobile phase flow rate was set at 0.5, 0.6, 0.8, and 1.0 ml/min. Catechin and epicatechin in cacao samples was detected by mass spectrometry. Condition of mass spectrometer was run by varying ESI voltage, nebulizer pressure, desolvation temperature, and desolvation gas. Validations test included some parameters such as specificity/ selectivity, linearity of calibration curve, limit of detection and limit of quantitation, precision and recovery test. Samples taken during the process were cacao nib, cacao mass, cacao powder and cacao butter.The results of this study showed that analytical conditions for catechin and epicatechin were using mobile phase A (0.1 % formic acid in deionized water) and mobile phase B (acetonitril-methanol - 50:50) at flow rate of 0.5 ml/min. Gradient elution were set at 0 minutes (10% B), 15 minutes (35% B), 20 minutes (40% B), 30 minutes (50% B), 35 minutes (60% B), and 35.1 minute (10% B). Mass spectrometer was set at ESI voltage (-) 3500 volt, desolvation temperature 300 °C, nebulizer pressure 50 psi, desolvation gas 10 L/min, and fragmentor voltage (-) 160 volt. Limit of detection and limit of quantitation of catechin were 0.28 and 0.93 ppm, respectively, while epicatechin were 7.15 and 23.84 ppm, respectively. Based on concentrations of catechin and epicatechin, heat treatment during cacao mass Processing showed a decrease tendency of catechin and epicatechin ratios."

"O6-Metilguanin dan N7-metilguanin merupakan isomer DNA adduct. N7-Metilguanin memberikan efek sitotoksik, sedangkan O6-metilguanin memberikan efek mutagenik yang dapat memicu timbulnya kanker sekunder. Kedua senyawa tersebut sering ditemukan dalam kadar yang sangat rendah pada pasien kanker yang memperoleh agen pengalkilasi sebagai terapi antikankernya. Oleh karena itu untuk menganalisis kedua senyawa tersebut dibutuhkan metode analisis yang memiliki selektivitas dan sensitivitas yang sangat tinggi. Pada penelitian ini dilakukan optimasi dan validasi metode analisis O6-metilguanin dan N7- metilguanin secara kromatografi cair kinerja ultra tinggi - tandem spektrometri massa. Kondisi analisis yang optimal diperoleh dengan sistem kromatografi: kolom C18 Acquity BEH (1,7 µm, 100 mm × 2,1 mm); fase gerak larutan asam asetat 0,05% - asetonitril (95:5 v/v); laju alir 0,3 mL/menit; dan deteksi diatur pada m/z 166,10 > 149,10 dan 166,10 > 134,10 untuk O6-metilguanin, serta m/z" 166,10 > 149,10 dan 166,10 > 96,10 untuk N7-metilguanin. Metode yang diperoleh valid dengan hasil kurva kalibrasi yang linier (r > 0,999) baik untuk O6- metilguanin dan N7-metilguanin; presisi dengan nilai koefisien variasi (KV) sebesar < 6,54% untuk O6-metilguanin dan < 3,17% untuk N7-metilguanin; serta akurat dengan nilai perolehan kembali pada empat konsentrasi sebesar 90,52-109,65% untuk O6-metilguanin dan 93,77%-106,65% untuk N7-metilguanin. Nilai LLOQ untuk O6-metilguanin dan N7-metilguanin berturut-turut sebesar 0,5 ng/mL dan 1,0 ng/mL. Nilai LLOQ tersebut menunjukkan bahwa metode ini sangat sensitif.

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O6-Methylguanine and N7-methylguanine are isomer of DNA adduct. N7- Methylguanine has cytotoxic effect, whereas O6-methylguanine has mutagenic effect which vulnerably leads to secondary cancer. The compounds were commonly found at very low concentration in cancer patients who had been receiving alkylating agent as their anticancer therapy. Therefore, the very selective and sensitive analytical method is needed to analyze those compounds. In this research, the optimization and validation of analytical method for analysis of O6-methylguanine and N7-methylguanine by ultra high performance liquid chromatography - tandem mass spectrometry was performed. Optimal analytical condition was obtained by system of chromatography: Acquity BEH C18 column (1.7 µm, 100 mm × 2.1 mm); mobile phase of 0.05% acetic acid - acetonitrile (95:5 v/v); flow rate of 0.3 mL/min; and detection was set at m/z 166.10 > 149.10 and 166.10 > 134.10 for O6-methylguanine, and at m/z 166.10 > 149.10 and" 166.10 > 96.10 for N7-methylguanine. The method is valid by the calibration curve with good linearity (r > 0.999) for both of O6-methylguanine and N7- methylguanine; precision by the coefficient of variation (CV) was < 6.54% for O6-methylguanine and < 3.12% for N7-methylguanine; and accurate by the recovery for four concentrations ranged from 90.52-109.65% for O6- methylguanine and 93.77-106.65% for N7-methylguanine. LLOQ values for O6- methylguanine and N7-methylguanine were found to be 0.5 ng/mL and 1.0 ng/mL, respectively. Those LLOQ values indicated that the method was very sensitive.""

"6-Merkaptopurin (6-MP) merupakan agen kemoterapi kanker yang termasuk dalam golongan antimetabolit antagonis purin. 6-Merkaptopurin harus melalui jalur metabolisme oleh tiopurin S-metiltransferase (TPMT) untuk menjadi metabolit inaktifnya, yaitu 6-metilmerkaptopurin (6-MMP) untuk mengurangi efek sitotoksik dari 6-MP yang dapat menyebabkan mielosupresi. Penelitian ini bertujuan untuk memperoleh metode optimum dan tervalidasi dalam menganalisis 6-MP dan 6- MMP secara simultan dalam sampel Dried Blood Spot menggunakan kromatografi cair kinerja ultra tinggi tandem spektrometri massa. Larutan kontrol kualitas dan kurva kalibrasi dibuat dengan menotolkan masing-masing sebanyak 40 μL pada kertas CAMAG DBS dan dikeringkan selama 3 jam. Kertas DBS dipotong dengan diameter 8 mm dan diekstraksi dengan larutan asetonitril-metanol (1:3) yang mengandung baku 5-fluorourasil (5-FU). Pemisahan dilakukan dengan kolom Waters Acquity UPLC Class BEH C18 1,7 μm (2,1 x 100 mm) dengan fase gerak berupa asam format 0,1% dalam air - asam format 0,1% dalam asetonitril dengan gradient elusi dan laju alir 0,2 mL/menit. Deteksi massa dilakukan dengan Waters Xevo TQD dengan Electrospray Ionization (ESI) positif untuk 6-MP dan 6-MMP dan ESI negative untuk 5-FU pada mode Multiple Reaction Monitoring. Deteksi 6- MP, 6-MMP, 5-FU berturut-turut adalah 153,09 > 119,09; 167,17 > 126,03; 129,09 > 42,05. Metode ini linear dalam rentang 26 ? 1000 ng/mL untuk 6-MP dan 13 - 500 ng/mL untuk 6-MMP dengan r berturut-turut adalah ≥ 0,998 dan ≥ 0,999. Nilai % diff dan koefisien variasi (KV) untuk akurasi dan presisi intra hari dan antar hari tidak lebih dari 15% dan tidak lebih dari 20% pada konsentrasi LLOQ. Metode ini memenuhi persyaratan selektivitas, linearitas, akurasi, presisi, carry-over, dan efek matriks yang mengacu pada EMEA Guidelines.

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6-Mercaptopurine (6-MP) is a cancer chemotherapeutic agent that belongs to a class of purine antagonist antimetabolite. 6-Mercaptopurine has to go through the metabolic pathway by thiopurine S-methyltransferase (TPMT) to become its inactive metabolite, 6-methylmercaptopurine (6-MMP) to reduce the cytotoxic effect of 6-MP which can cause myelosuppression. This study aimed to obtain an optimum and validated method in analyzing 6-MP and 6-MMP simultaneously in Dried Blood Spot samples using ultra high-performance liquid chromatography tandem mass spectrometry. The quality control and calibration curves solutions were made by respectively spot 40 μL at DBS CAMAG paper and dried for 3 hours. DBS papers were cut with a diameter of 8 mm and extracted with acetonitrilemethanol (1:3) containing internal standard 5-fluorouracil (5-FU). Separation was performed with Waters Acquity UPLC BEH C18 column Class 1.7 μm (2.1 x 100 mm) with a mobile phase consists of 0.1% formic acid in water ? 0.1% formic acid in acetonitrile with gradient elution and flow rate 0.2 mL/minute. Mass detection was done using Waters Xevo TQD with positive electrospray ionization (ESI) for 6-MP and 6-MMP and negative ESI for 5-FU in Multiple Reaction Monitoring mode. Detection of 6-MP, 6-MMP, 5-FU respectively was 153.09> 119.09; 167.17> 126.03; 129.09> 42.05. This method is linear with the range 26-1000 ng / mL for 6-MP and 13 to 500 ng / mL for 6-MMP with consecutive r value is ≥ 0,998 and ≥ 0,999. % Diff value and coefficient of variation (CV) for accuracy and precision of intra-day and inter-day are not more than 15% and not more than 20% at a concentration LLOQ. This method fulfilled the requirements of selectivity, linearity, accuracy, precision, carry-over, and matrix effects which refers to the EMEA Guidelines."

"Risperidon (RIS) merupakan obat golongan antipsikotik generasi kedua yang bekerja dengan cara memblok reseptor serotonin (5-HT2A) dan dopamin (D2). RIS dan metabolit aktifnya, yaitu 9-Hidroksirisperidon (9-OH-RIS), menunjukkan tingkat variabilitas berdasarkan polimorfisme CYP2D6, sehingga berdampak pada variabilitas efektivitas terapi dan efek samping obat. Penelitian ini bertujuan untuk memperoleh metode analisis yang optimum dan tervalidasi terhadap RIS dan 9-OH-RIS dalam Dried Blood Spot menggunakan Kromatografi Cair Kinerja Ultra Tinggi – Tandem Spektrometri Massa. Preparasi sampel dilakukan dengan larutan pengekstraksi metanol–asetonitril dengan metode ekstraksi sonicated-assisted extraction. Pemisahan dilakukan dengan fase gerak asam format 0,1%–metanol 15:85, elusi isokratik, dan laju alir 0,1 mL/menit. Analisis kuantitatif menggunakan spektrometri massa dengan ESI positif serta mode analisis MRM. Deteksi RIS, 9-OH-RIS, dan Clozapin berturut-turut adalah 411,16 --> 191,12; 427,16 --> 207,11; dan 327,10 --> 270,10. Nilai LLOQ RIS dan 9-OH-RIS didapatkan sebesar 2,0 ng/mL. Nilai %KV dan %diff pada within run dan between run tidak lebih dari 15% pada QC dan tidak lebih dari 20% pada LLOQ. Hasil validasi menunjukkan hasil yang sensitif, selektif, dan valid untuk bioanalisis kadar RIS dan 9-OH-RIS dalam darah sesuai guideline FDA tahun 2018.

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isperidone (RIS) is a secondary generation antipsychotics drug that works by blocking serotonin (5-HT2A) and dopamine (D2) receptors. RIS and its active metabolite, 9-Hydroxyrisperidone (9-OH-RIS) showed a variability based on the CYP2D6 polymorphism, thus impacting variability in therapeutics efficacy and drug side-effects. This study aimed to obtain an optimum and validated analytical method for RIS and 9-OH-RIS in Dried Blood Spot using Ultra High Performance Liquid Chromatography – Tandem Mass Spectrometry. Sample preparation was carried out using methanol–acetonitrile extraction solution by sonicated-assisted extraction method. Separation was carried out using a mobile phase consist of 0.1% formic acid– methanol 15:85, isocratic eluti,on and flow rate of 0.1 mL/minute. Quantitative analysis was carried out using mass spectrometry with ESI positive and MRM analysis mode. Detection of RIS, 9-OH-RIS, and Clozapine were 411.16 --> 191.12; 427.16 --> 207.11; and 327.10 --> 270.10. The LLOQ of RIS and 9-OH-RIS was the same, 2.0 ng/mL . The value of %CV and %diff at within-run and between-run were no more than 15% for QC and not more than 20% at LLOQ. The validated result performed sensitive, selective, and valid for bioanalysis of RIS and 9-OH-RIS levels in the blood according to the 2018 FDA guidelines."

"Siklofosfamid merupakan agen kemoterapi kanker yang memerlukan bioaktivasi oleh sitokrom P450 menjadi metabolit aktifnya yaitu 4-hidroksisiklofosfamid untuk menghasilkan efek sitotoksik. Penelitian ini bertujuan untuk memperoleh metode yang optimum dan tervalidasi dalam menganalisis siklofosfamid dan 4- hidroksisiklofosfamid secara simultan dalam plasma menggunakan metode kromatografi cair kinerja ultra tinggi tandem spektrometri massa. Pemisahan dilakukan dengan kolom Waters Aqcuity UPLC Class BEH C18 1,7 μm (2,1 x 100 mm) yang dilindungi prekolom VanGuardTM BEH 1,7 μm dengan fase gerak berupa asam format 0,1% - metanol dengan gradien elusi dan laju alir 0,2 mL/menit. Deteksi massa dilakukan dengan Waters Xevo TQD tipe Electrospray Ionization (ESI) positif pada mode Multiple Reaction Monitoring. Siklofosfamid dideteksi pada m/z 260,968 > 139,978; 4-hidroksisiklofosfamid-semikarbazida pada 338,011 > 224,979; dan parasetamol sebagai baku dalam pada 152,040 > 109,779. Senyawa 4-hidroksisiklofosfamid sangat tidak stabil dalam plasma dan karenanya diperlukan proses derivatisasi terlebih dulu. Derivatisasi dilakukan dengan semikarbazida-hidroklorida 2 M dalam dapar kalium fosfat 50 mM pH 7,4. Sampel plasma sebanyak 250 μL yang telah diderivatisasi diekstraksi menggunakan 1 mL etil asetat, dilakukan pencampuran putar, dan sentrifugasi pada 3.000 rpm selama 10 menit. Metode ini linear pada rentang 50 ? 10.000 ng/mL dengan r ≥ 0,9999 untuk siklofosfamid dan 5 ? 500 ng/mL dengan r ≥ 0,9994 untuk 4-hidroksisiklofosfamid. Nilai % diff dan koefisien variasi (KV) untuk akurasi dan presisi intra hari dan antar hari selama tiga hari tidak lebih dari 15% dan tidak lebih dari 20% pada konsentrasi LLOQ. Secara keseluruhan, metode ini memenuhi persyaratan selektivitas, linearitas, akurasi, presisi, carry over, dan efek matriks sesuai EMEA Guidelines.

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Cyclophosphamide is an agent for cancer chemotherapy that requires bioactivation by cytochrome P450 to its active metabolite, 4-hydroxycyclophosphamide, to manifest its cytotoxic activity. The aim of this reasearch is to develop an optimum and validated method on analyzing cyclophosphamide and 4-hydroxycyclophosphamide simultaneously using ultra performance liquid chromatography tandem mass spectrometry. Chromatographic separation was achieved by a Waters Acquity UPLC Class BEH C18 column (1.7 μm, 50 mm x 2.1 mm) protected by a VanGuardTM BEH 1.7 μm precolumn. The mobile phase consisted of formic acid 0.1% and methanol under gradient elution and flow rate of 0.2 mL/min. Mass detection was performed on Waters Xevo TQD equipped with an electrospray ionization (ESI) source at positive ion mode in the multiple reaction monitoring (MRM) mode. Cyclophosphamide was detected at m/z 260.968 > 139.978, 4-hydroxycyclophosphamide-semicarbazide at m/z 338.011 > 224.979, and paracetamol as internal standard at m/z 152.040 > 109.779. Due to the highly instability of 4-hydroxycyclophosphamide in plasma, it is necessary to undergo derivatization process. Derivatization was performed by 2 M semicarbazide hydrochloride that was diluted with 50 mM potassium phosphate buffer pH 7.4. Plasma was extracted using 1 mL ethyl acetate, followed by whirl-mixing for 2 minutes, and centrifuged at 3000 rpm for 10 minutes. This method fulfill the acceptance criteria of linearity in range of 50 ? 10.000 ng/mL with r ≥ 0.9999 for cyclophosphamide and 5 ? 500 ng/mL with r ≥ 0.9994 for 4-hydroxycyclophosphamide. This method also fulfill the acceptance criteria for accuracy and precision within and between run in three days by % diff and coefficient of variation (CV) not more than 15% and not more than 20% for LLOQ concentration. Overall, this method fulfill the acceptance criteria for selectivity, linearity, accuracy, precision, carry over, and matrix effect based on EMEA Guidelines."

"Siklofosfamid adalah kemoterapi yang bekerja sebagai agen pengalkilasi dan merupakan prodrug sehingga membutuhkan aktivasi oleh enzim sitokrom P450 untuk berubah menjadi metabolit aktifnya, yaitu 4-hidroksisiklofosfamid 4-OHCP. Tujuan penelitian ini adalah untuk memperoleh metode optimum dan tervalidasi untuk analisis siklofosfamid dan 4-OHCP dalam dried blood spot menggunakan Kromatografi Cair Kinerja Ultra Tinggi-Tandem Spektrometri Massa KCKUT-SM/SM. Penelitian siklofosfamid dan 4-hidroksisiklofosfamid secara simultan ini dikembangkan pertama kalinya dalam sampel dried blood spot. Metabolit 4-OHCP bersifat tidak stabil dalam cairan biologis, sehingga prosedur derivatisasi dilakukan sebelum analisis, yaitu menggunakan semikarbazid hidroklorida. Pemisahan dilakukan pada kolom UPLC Class BEH C18 menggunakan fase gerak asam format 0,01 dalam air-metanol 50:50 dengan mode elusi isokratik pada laju alir 0,3 mL/menit selama 4 menit. Deteksi massa dilakukan pada Waters Xevo TQD dengan Electrospray Ionization positif untuk siklofosfamid, 4-OHCP, dan heksametilfosforamid sebagai baku dalam dengan nilai m/z berturut-turut adalah 260,968 > 139,976; 338,011 > 224,979; dan 180,17 > 92,08. Ekstraksi dilakukan menggunakan metode pengendapan protein dengan pelarut metanol ? ?asetonitril 2:1. Metode ini linear pada rentang 50-30.000 ng/mL untuk siklofosfamid dan 10-1.000 ng/mL untuk 4-OHCP dengan r berturut-turut adalah 0,9972 dan 0,9984. Nilai LLOQ untuk siklofosfamid dan 4-OHCP berturut-turut adalah 50 ng/mL dan 10 ng/mL. Nilai diff dan KV untuk akurasi dan presisi intra hari dan antar hari tidak melebihi 15 dan tidak melebihi 20 pada konsentrasi LLOQ. Secara keseluruhan metode ini telah memenuhi persyaratan validasi yang mengacu pada European Medicines Agency Guidelines 2011.

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Cyclophosphamide is a chemotherapy that acts as an alkylating agent and a prodrug that requires activation by the cytochrome P450 enzyme to convert into its active metabolite, 4 hydroxycycrophosphamide 4 OHCP. The purpose of this research is to obtain the optimum and validated method for the analysis of cyclophosphamide and 4 OHCP in dried blood spots using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry UPLC MS MS. This simultaneous cyclophosphamide and 4 OHCP study was developed for the first time in dried blood spot sample. The 4 OHCP metabolite is unstable in biological fluids, so the derivatization procedure was performed prior to analysis, using semicarbazide hydrochloride. The separation was performed on UPLC Class BEH C18 column using mobile phase of 0.01 formic acid in water methanol 50 50 with isocratic elution mode at 0.3 mL minute for 4 min. Mass detection was performed on Waters Xevo TQD with Positive Electrospray Ionization for cyclophosphamide, 4 OHCP, and hexamethylphosphoramide as internal standard with m z values respectively are 260.968 139.976 338.011 224.979 and 180.17 92.08. Extraction was performed using protein precipitation method with methanol acetonitrile 2 1. This method was linear in the range of 50 30,000 ng mL for cyclophosphamide and 10 1,000 ng mL for 4 OHCP with r respectively are 0.9972 and 0.9984. The LLOQ values for cyclophosphamide and 4 OHCP were 50 ng mL and 10 ng mL. The value of diff and CV for accuracy and precision intra days and between days did not exceed 15 and did not exceed 20 of LLOQ concentrations. Overall this method has met the validation requirements that refer to European Medicines Agency Guidelines 2011."

"Ivermectin merupakan obat yang digunakan secara luas untuk mengendalikan dan mengobati spektrum luas infeksi yang disebabkan oleh parasit nematoda khususnya onchocerciasis. Oleh karena ivermectin didisain untuk obat cacing, maka kadar diusahakan tinggi di saluran cerna, sehingga yang masuk sistemik rendah. Kadar ivermectin yang sangat kecil, memerlukan metode analisis yang sensitif dan selektif. Penelitian ini bertujuan untuk mendapatkan metode analisis yang sensitif dan selektif serta tervalidasi menggunakan Kromatografi Cair Kinerja Ultra Tinggi – tandem Spektrometri Massa (KCKUT-SM/SM). Analisis ivermectin dilakukan dengan menggunakan kolom C18 Acquity® Bridged Ethylene Hybrid (BEH) 1,7 μm, 100 x 2,1 mm. Matriks biologi yang digunakan plasma dengan baku dalam doramectin. Preparasi sampel menggunakan pelarut pengendapan protein yaitu campuran metanol dan asetonitril dengan perbandingan (1:1 v/v). Kondisi analisis optimum diperoleh dengan fase gerak berupa amonium format 5mM pH 3 – asetonitril (10:90 v/v) dengan laju alir 0,2 mL/menit dan dielusi secara isokratik selama 5 menit. Kuantifikasi analisis dilakukan menggunakan spektrometri massa triple quandrupole dengan mode electrospray ionization (ESI) positif; deteksi pada m/z 892,41 > 569,5 untuk ivermectin dan m/z 916,41 > 331,35 untuk doramectin. Metode analisis tervalidasi mengikuti pedoman US Food and Drug Adminitration (FDA) tahun 2018 dengan rentang konsentrasi linear pada 0,5-200 ng/ml.

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Ivermectin is a drug that is widely used to control and treat a broad spectrum of infections caused by parasitic nematodes, especially onchocerciasis. Because ivermectin is designed for deworming, then the concentration must be higher in the gastrointestinal tract so that what goes into systemic is low. Low levels of ivermectin in plasma require sensitive and selective analytical methods. This study aims to obtain a sensitive, selective, and validated analytical method using Ultra-High Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-/MS/MS). Ivermectin analysis was performed using a C18 Acquity® Bridged Ethylene Hybrid (BEH) column of 1.7 μm; 100 x 2.1 mm. The biological matrix used was plasma with doramectin as the internal standard. Sample preparation used a protein precipitation solvent in the form of a mixture of methanol and acetonitrile with a ratio (1:1 v/v). The optimum analysis conditions were obtained in the mobile phase of the combination ammonium formate 5mM pH 3 – acetonitrile (10:90 v/v) with a flow rate of 0.2 mL/minute and eluted isocratically for 5 minutes. Quantification analysis was performed using triple quadrupole mass spectrometry with positive electrospray ionization (ESI) mode; detection at m/z 892.41 > 569.5 for ivermectin and m/z 916.41 > 331.35 for doramectin. The validated analytical method follows the 2018 US Food and Drug Administration (FDA) guidelines with a linear concentration range of 0.5-200 ng/ml."

"Tafenokuin adalah obat antimalaria golongan 8-aminoquinoline yang disetujui oleh the United States Food and Drug Administration (US FDA) pada tahun 2018 untuk radical cure dan profilaksis malaria. Metode analisis tafenokuin yang ada umumnya menggunakan baku dalam berupa stable isotope-labeled (SIL)-tafenokuin, yang mahal, sehingga diperlukan pengembangan metode analisis yang lebih ekonomis. Penelitian ini bertujuan untuk mengembangkan metode analisis tafenokuin dalam plasma yang optimal, valid, dan lebih terjangkau dengan menggunakan primakuin, obat antimalaria sejenis, sebagai baku dalam. Metode ini menggunakan sistem Kromatografi Cair Kinerja Ultra Tinggi-Tandem Spektrometri Massa (KCKUT-SM/SM). Preparasi sampel dilakukan melalui presipitasi protein dengan asetonitril sebagai pelarut organiknya. Pemisahan dilakukan dengan kolom Shim-pack XR-ODS III (2,0 x 50 mm; 1,6 μm) dengan laju alir 0,5 mL/menit dan fase gerak asetonitril serta asam format 0,1% secara elusi gradien. Deteksi analit menggunakan spektrometri massa triple quadrupole dalam mode electrospray ionization (ESI) positif dan multiple reaction monitoring (MRM) dengan m/z 464,3>447,2 untuk tafenokuin dan 260,25>243,1 untuk primakuin. Metode ini mencapai batas kuantifikasi terendah 1 ng/mL untuk tafenokuin dan terbukti valid, sensitif, serta selektif untuk analisis tafenokuin dalam plasma sebagai alternatif yang lebih ekonomis dibandingkan metode berbasis SIL-tafenokuin.

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Tafenoquine, an 8-aminoquinoline antimalarial drug, was approved by the United States Food and Drug Administration (US FDA) in 2018 for radical cure and malaria prophylaxis. Traditional methods for analyzing tafenoquine rely on stable isotope-labeled (SIL) tafenoquine as internal standards, which are costly, prompting the need for a more economical alternative. This study developed a cost-effective and validated method to analyze tafenoquine in plasma using primaquine, another antimalarial drug in the same class, as the internal standard. The method utilizes Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) with protein precipitation using acetonitrile for sample preparation. Separation is achieved with a Shim-pack XR-ODS III column (2.0 x 50 mm; 1.6 μm) at a 0.5 mL/min flow rate, employing gradient elution with acetonitrile and 0.1% formic acid. Detection uses triple quadrupole mass spectrometry in positive electrospray ionization (ESI) mode with multiple reaction monitoring (MRM) at m/z 464.3>447.2 for tafenoquine and 260.25>243.1 for primaquine. This method achieves a lower limit of quantification of 1 ng/mL for tafenoquine and is validated as sensitive, selective, and accurate for plasma analysis, offering a more accessible alternative to SIL-tafenoquine-based methods."

"Akrilamida merupakan senyawa karsinogen yang dapat ditemukan pada makanan, kopi, dan asap rokok. Ketika masuk ke dalam tubuh manusia, akrilamida akan dimetabolisme oleh CYP2E1 menjadi glisidamida yang kemudian dapat bereaksi dengan DNA membentuk DNA adduct. Analisis akrilamida dan glisidamida secara simultan dalam darah, teknik biosampling yang biasa digunakan adalah venipuncture yang bersifat invasif dan membutuhkan keahlian khusus. Pada penelitian ini, teknik biosampling yang digunakan adalah dried blood spot (DBS) yang mudah dan tidak invasif. Metode untuk menganalisis akrilamida dan glisidamida secara simultan menggunakan DBS belum pernah dilakukan pada penelitian sebelumnya. Maka, penelitian ini bertujuan untuk mendapatkan metode analisis akrilamida dan glisidamida secara simultan yang optimal dan tervalidasi dengan menggunakan propanamida sebagai standar internal. Sampel dipreparasi dengan pengendapan protein menggunakan metanol dan air (1:1). Pemisahan senyawa menggunakan kromatografi fase terbalik dengan kolom Acquity® UPLC BEH C18 (1,7 μm; 2,1 mm x 100 mm), dielusi dengan laju alir 0,20 mL/min dengan kondisi gradien dengan fase gerak 0,2% asam formiat dalam air dan asetonitril selama 5 menit. Deteksi analit dilakukan menggunakan spektrometri massa triple quadrupole dengan mode electrospray ionization positif dan multiple reaction monitoring (MRM) diatur pada m/z 72,0 > 55,02 untuk akrilamida, 88,1 > 44,0 untuk glisidamida, dan 74,01 > 57,1 untuk propanamida. Batas kuantitasi terendah yang diperoleh adalah 1 µg/ml untuk akrilamida dan glisidamida. Rentang konsentrasi linier antara 1 - 40 µg/ml. Metode analisis tervalidasi sesuai pedoman FDA 2018.

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Acrylamide is a carcinogenic compound that can be found in food, coffee, and cigarette smoke. When it enters the human body, acrylamide will be metabolized by CYP2E1 to glycidamide which can then react with DNA to form DNA adducts. To analyze acrylamide and glycidamide simultaneously in the blood, the biosampling technique commonly used is venipuncture which is invasive and requires special expertise. In this study, the biosampling technique used is dried blood spot (DBS) which is easy and non-invasive. Methods for analyzing acrylamide and glycidamide simultaneously using DBS have not been carried out in previous studies. Therefore, this study aims to obtain an optimal and validated method of acrylamide and glycidamide simultaneous analysis using propanamide as an internal standard. Samples were prepared by protein precipitation using methanol and water (1: 1). Separation of compounds used reverse phase chromatography with the Acquity® UPLC BEH C18 column (1.7 μm, 2.1 mm x 100 mm), eluted at a flow rate of 0.20 mL/min under gradient conditions with a mobile phase of 0.2% formic acid in water and acetonitrile for 5 minutes. Quantification was performed using triple quadrupole mass spectrometry with positive electrospray ionization and multiple reaction monitoring (MRM) mode set at m / z 72.0> 55.02 for acrylamide, 88.1> 44.0 for glycidamide, and 74.01> 57.1 for propanamide. The lowest limit of quantification is obtained at 1 μg / ml for both acrylamide and glycidamide. The range of linear concentration is between 1 - 40 µg / ml. The analysis method is validated according to FDA 2018 guidelines."