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"Until nowadays study of drug profile inside body (pharmacokinetic) and its development is still an interesting topic under pharmaceutical service. Development of an accurate analysis method for small quantity of drug in blood is an important step, HPLC method usually recommended for this purpose. Observation in studying the optimal method to analyze drug in human blood by using internalstandard has been done for meloxicam, a new generation of NSAID. Two things has been focused to this observation, finding an ideal internal standard for meloxicam and testing the recovery of meloxicam in blood sample by in vitro. Coefficient of distribution of many samples (piroxicam, trimetropim, caffeine, salisilamid) givescaffeine as recommended internal standard for meloxicam. The recovery test gives 83,58% ± 3,802%, 74,37% ± 0,711%, 82,14% ± 1,937% for analysis meloxicam in human blood without internal standard; and 41,58% ± 1,108%, 61,60% ± 1,049%, 56,88% ± 0,478% for analysis meloxicam in human blood within internal standard."

"Cilostazol merupakan antiplatelet yang bekerja dengan menghambat fosfodiesterase III (PDE III). Berdasarkan Food and Drug Administration (FDA), cilostazol merupakan obat yang wajib untuk uji bioekuivalensi. Metode analisis menggunakan kromatografi cair kinerja tinggi (KCKT) dengan detektor ultraviolet untuk penentuan cilostazol dalam plasma manusia in vitro telah dikembangkan dan divalidasi. Cilostazol dan pioglitazone sebagai baku dalam diekstraksi dari plasma dengan metode pengendapan protein menggunakan metanol. Fase gerak terdiri dari asetonitril-dapar kalium dihidrogen fosfat 50 mM (40:60) dengan kecepatan alir 1,5 mL/menit, menggunakan kolom C18 (SunfireTM, 5 μ m, 250x4,6 mm) fase terbalik, dan dideteksi pada panjang gelombang 257 nm. Pada rentang konsentrasi 20 - 2000 ng/mL dihasilkan kurva kalibrasi yang linier dengan koefisien korelasi (r) 0,9999. Akurasi (% diff) dari metode ini -14,67% sampai 8,84% dengan presisi (KV) antara 0,98% sampai 4,93%, dan uji perolehan kembali absolute 82,26% sampai 119,85%. Cilostazol dalam plasma stabil selama 30 hari pada penyimpanan dengan suhu -20oC.

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Cilostazol is an antiplatelet agent with the mechanism of action by inhibiting phos-phodiesterase III (PDE III). Referred to Food and Drug Administration(FDA), cilostazol is a drug recommended to be bioequivalence (BE) studied. A high-performance liquid chromatographic (HPLC) method with ultraviolet detector for in vitro determination of cilostazol in human plasma had been developed and validated. Cilostazol and pioglitazone as internal standard were extracted from human plasma by protein precipitation method using methanol. The mobile phase consisting of acetonitrile-potassium di-hydrogen phosphate buffer 50 mM (40:60) was used at the flow rate of 1.5 mL/min on reversed phase C18 column (SunfireTM, 5μ m, 250x4.6 mm), and was detected at wavelength of 257 nm. Linearity was established within concentration range of 20-2000 ng/mL with coefficient correlation (r) was 0,9999. Accuracy (% diff) of this method was -14.67% up to 8.84% with precision (CV) being 0.98% to 4.93%, and absolute recovery was established to be 82.26% to 119.85%. Cilostazol in plasma was stable for 30 days in -20oC storage."

"Rebamipid tergolong suatu obat antiulkus yang masuk dalam kategori obat wajib uji Bioekivalensi (BE) menurut Food and Drug Administration (FDA). Penelitian ini bertujuan untuk memperoleh kondisi optimum untuk analisis rebamipid dalam plasma in vitro menggunakan Kromatografi Cair Kinerja Tinggi (KCKT) detektor ultraviolet dan melakukan validasi metode analisis tersebut. Kromatografi dilaksanakan dengan teknik isokratik pada kolom fase terbalik Kromasil® C18 (5 μm, Akzo Nobel) panjang kolom 250 x 4,6 mm, fase gerak asetonitril-dapar fosfat pH 3,0 (40:60), dengan kecepatan alir 1,0 ml/menit, dan dideteksi pada panjang gelombang 230 nm. Teknik penyiapan sampel dilakukan dengan cara ekstraksi cair-cair menggunakan asam fosfat dan etil asetat. Karbamazepin digunakan sebagai baku dalam. Metode ini valid menurut FDA dalam Bioanalytical Method Validation, dengan nilai koefisien korelasi r = 0,9993 dan linier pada kisaran konsentrasi 0,04 ? 1,2 ìg/ml, batas terendah kuantitasi (LLOQ) 42,0 ng/ml, presisi kurang dari 6%, dan nilai perolehan kembali antara 90,32 sampai 113,45%. Rebamipid stabil dalam plasma selama 14 hari penyimpanan pada suhu -200C.

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Rebamipide is antiulcer agent and it is one of the drug that have to be evaluated with bioequivalency test according to Food and Drug Administration (FDA). The objective of this research is to find out the optimum condition of rebamipide in human plasma in vitro analysis by High Performance Liquid Chromatography (HPLC) with ultraviolet detector, and then the method was validated. The chromatography was carried out by isocratic technique on a reversed-phase Kromasil® C18 (5 μm, Akzo Nobel), column length was 250 x 4.6 mm, with mobile phase consisted of acetonitrile - phosphate buffer pH 3.0 (40:60) at flow rate of 1.0 ml/min, and detection was performed at wavelength of 230 nm. The sample preparation technique was liquidliquid extraction by phosphoric acid and ethyl acetate. Carbamazepine was used as the internal standard. The method was valid according to FDA in Bioanalitycal Method Validation, with coefficient correlation of 0.9993 and linear in the range concentration of 0.04 ? 1.2 μg/ml, the lower limit of quantitation was 42.0 ng/ml, precision less than 6% and recovery percentage was 90.32 to 113.45%. Rebamipide in plasma was stable for 14 days storage in -200C."

"The determination of pseudoephedrine hydrochloride and triprolidine hydrochloride in influenza syrup medicine has been performed using TLC densitometric method. Pseudoephedrine hydrochloride and triprolidine hydrochloride were extracted using chloroform at pH 12 from the syrup, and separated using HPTLC silica Kieselguhr glass plates 60 F 254, 20x10 cm2 as stationary phase, and a mixture of methanol, ammonia and chloroform (40:2:30) as mobile phase. The plates were analyzed using Camag TLC Scanner 3 with UV-detector at 257 nm for pseudoephedrine hydrochloride and at 290 nm for triprolidine hydrochloride. The results showed that the linearity, limit of detection, and limit of quantitation of the method for pseudoephedrine hydrochloride were 0.9999, 0.0064 ìg, and 0.2124 ìg respectively; while for triprolidine hydrochloride were 0.9999, 0.0076 ìg, and 0.0254 ìg respectively. The coefficient of variance (CV) of repeatability for the two substances were less than 2.0%; and the recovery values for pseudoepherine hydrochloride and triprolidine hydrochloride were 99.98 + 1.05% and 99.73 + 1,54% respectively. The result showed that the samples analysed contained pseudoephedrine hydrochloride 94.36% of the labeled ammount, and triprolidine hydrochloride 94.44% of the labeled ammount."

"Esomeprazol merupakan salah satu obat penghambat pompa proton yang efektif untuk mempertahankan pH lambung. Esomeprazol dibuat dalam bentuk tablet salut selaput sehingga termasuk obat wajib Uji Bioekivalensi menurut Peraturan Kepala Badan Pengawas Obat dan Makanan Republik Indonesia tentang Obat Wajib Uji Ekivalensi. Uji Bioekivalensi obat harus menggunakan metode bioanalisis yang tervalidasi. Penelitian ini bertujuan untuk mengembangkan metode analisis esomeprazol dalam plasma mulai dari kondisi kromatografi optimum, metode preparasi plasma optimum, hingga validasi metode analisis. Kondisi kromatografi optimum adalah kolom C-18 (Waters, SunfireTM 5 µm; 250 x 4,6 mm), suhu kolom 40°C; fase gerak asetonitril - dapar fosfat pH 7,6 (40 : 60 %v/v); laju alir 1,00 mL/menit; detektor photodiode array pada panjang gelombang 300 nm; dan lansoprazol sebagai baku dalam. Preparasi sampel menggunakan metode ekstraksi cair-cair dengan pelarut diklorometan lalu dikeringkan dengan gas nitrogen pada suhu 40°C selama 30 menit; dan direkonstitusi dengan fase gerak sebanyak 100 µL. Hasil validasi terhadap metode analisis esomeprazol yang dilakukan memenuhi persyaratan validasi berdasarkan EMEA Bioanalytical Guideline tahun 2011. Metode yang diperoleh linear pada rentang konsentrasi 5,0 - 450,0 ng/mL dengan r > 0,9997.

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Esomeprazole is a proton pump inhibitor drug that is effective to maintain the pH of the stomach. Esomeprazole was formulated as film coated tablet that includes mandatory drug testing bioequivalence according to Regulation Head of National Agency of Drug and Food of the Republic of Indonesia about Mandatory Drug Testing equivalences. Drug bioequivalence trials should use validated bioanalytical method. This research aimed to develop analytical methods esomeprazole in human plasma from optimum chromatographic conditions, the optimum plasma preparation method, until the validation of analytical methods. The optimum chromatographic condition was obtain using C-18 column (Waters, Sunfire? 5 μm; 250 x 4.6 mm), column temperature 40°C; mobile phase acetonitrile - phosphate buffer pH 7.6 (40: 60% v/v); a flow rate of 1.00 mL/min; photodiode array detector at a wavelength of 300 nm; and lansoprazole as internal standard. Sample preparation using liquid-liquid extraction with dichloromethane as solvent and then dried with nitrogen gas at a temperature of 40°C for 30 minutes; and reconstituted with mobile phase of 100 mL. The results of validation fulfilled the acceptance criteria of validation method based on EMEA Bioanalytical Guideline 2011. The method was linear at concentration range of 5.0 to 450.0 ng / mL with r > 0.9997."

"ABSTRAKPengobatan hipertensi merupakan salah satu pendekatan untuk mengurangi risiko penyakit kardiovaskular, seperti pengobatan farmakologis menggunakan amlodipin besilat dan valsartan. Obat antihipertensi merupakan obat untuk kondisi serius sehinggaperlu dilakukan uji ekivalensi in vivo. Uji bioekivalensi untuk pengembangan obat generik dilakukan dalam jangka waktu yang cukup panjang sehingga perlu diketahui stabilitas in vivo amlodipin besilat dan valsartan dengan melakukan pengujian incurred sample stability. Penelitian ini bertujuan untuk menganalisis stabilitas in vivo amlodipin besilat dan valsartan dalam plasma 6 subjek sehat di hari ke-7, 14 dan 30 pada fase Cmax dan fase eliminasi. Analisis amlodipin besilat dan valsartan dilakukan terhadap 6 subjek sehat yang mengonsumsi tablet kombinasi dosis tetap amlodipin besilat 10 mg danvalsartan 160 mg. Pengambilan darah subjek dilakukan sebanyak 18 titik pada beberapa interval waktu hingga jam ke-72. Kondisi kromatografi yang digunakan adalah kolom Acquity UPLC BEH C18 (2,1 × 100 mm× 1,7 μm); dengan suhu kolom 45oC; fase gerak asetonitril dan asam format 0,1% dalam air dengan kondisi gradien; laju alir 0,2 mL/menit dengan total waktu analisis 6 menit. Deteksi massa dilakukan dengan Water Xevo TQD tipe Electrospray Ionization (ESI) positif pada mode Multiple ReactionMonitoring. Profil farmakokinetika dalam sampel plasma memberikan hasil: Cmax 4,86 - 6,56 ng/mL; tmax rata-rata 5,33 jam untuk amlodipin besilat dan Cmax 3570,00 - 4553,34 ng/mL; tmax rata-rata 4,17 jam untuk valsartan. Incurred sample stabilityamlodipin besilat dan valsartan pada plasma 6 subjek sehat sampai hari ke-30 menunjukkan hasil yang memenuhi persyaratan EMEA Bioanalytical Guideline tahun2011, dengan nilai %diff tidak lebih dari 20%.

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ABSTRACTHypertension therapy is one of the ways for reducing the cardiovascular diseases, such as pharmacology therapy using amlodipine besylate and valsartan. Antihypertensive agents are drugs for serious condition that need bioequivalence test. Bioequivalence testing for generic prodrug development is carried out in long period of time, so it is necessary that the stability of amlodipine besylate and valsartan to be known by analyzing the incurred sample stability. This study aimed to analyze the in vivo stability of amlodipine besylate and valsartan on subjects plasma samples on days 7, 14 and 30 in the Cmax phase and elimination phase. Amlodipine besylate and valsartan analysis were performed on 6 healthy subjects administered a fixed dose combination of amlodipine besylate and valsartan tablets that contain amlodipine besylate 10 mg and valsartan 160 mg. The subjects blood was collected in 18 points at several times up to 72 hours. The chromatographic conditions used was the Acquity UPLC BEH C18 column (2.1 × 100 mm × 1.7 μm); column temperature was 45oC; mobile phase consist of 0.1% acetonitrile and formic acid in water with gradient condition; flow rate 0.2 mL/minute with total run time of 6 minutes. Mass detection was performed using Waters Xevo TQD equipped with an electrospray ionization (ESI) source in positive mode with MRM mode. The pharmacokinetic profile in human plasma results were; Cmax 4.86 - 6.56 ng/mL; tmax 5.33 hours for amlodipine besylate and Cmax 3570.00 - 4553.34 ng/mL; tmax 4.17 hours for valsartan. The %diff values of amlodipine besylate and valsartan incurred sample stability until day 30 on 6 subjects not more than 20%, which fulfilled the acceptance criteria of validation method based on EMEA Bioanalytical Guideline 2011."

"Metode kromatografi cair kinerja tinggi (KCKT) dengan detektor fluoresensi untuk menganalisis ofloksasin dalam plasma telah dikembangkan. Tujuan dari penelitian ini adalah memperoleh kondisi yang optimum untuk analisis ofloksasin dalam plasma in vitro dan melakukan validasi metode analisis tersebut. Kondisi kromatografi menggunakan kolom C18 dengan fase gerak asetonitril-larutan kalium dihidrogen fosfat 0,01 M (140:860; v/v) pH 3, kecepatan alir 1,0 ml/menit dan dideteksi dengan detektor fluoresensi pada panjang gelombang eksitasi 300 dan emisi 500 nm. Siprofloksasin digunakan sebagai baku dalam. Teknik penyiapan sampel dilakukan dengan cara pengendapan protein menggunakan asetonitril, kemudian supernatannya dipisahkan lalu diinjeksikan ke dalam kolom. Metode ini memberikan nilai linearitas pada rentang konsentrasi 1,0 -5,0 g/ml dengan nilai koefisien korelasi (r) 0,9998. Batas deteksi pada metode ini konsentrasi 0,102 g/ml dan batas kuantitasi 0,340 g/ml. Metode ini memberikan hasil uji perolehan kembali pada konsentrasi 1,02 g/ml adalah 90,668 0,2635 %, konsentrasi 3,06 g/ml adalah 92,932 0,6468 % dan konsentrasi 5,1 g/ml adalah 95,594 3.184 %.

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A high-performance liquid chromatographic method (HPLC) with fluorescence detector for analyses of ofloxacin in human plasma was developed. The aim of this research is to find out optimum condition of ofloxacin in human plasma with in vitro analysis using High Performance Liquid Chromatography (HPLC) and then validate the method. Condition of chromatography using C18 column with a mixture of acetonitril-0,01 M dihydrogenpotassium phosphate solution (140:860) pH 3 as mobile phase, at flow rate 1,0 ml/menit, with fluorimetric detection was performed at 300 nm for excitation and 500 nm for emission. Ciprofloxacin was used as an internal standard. The sampel preparation technique was protein precipitation with acetonitril, the supernatant was desperated and injected into C18 column. Linearity was established for range of concentration 1.0-5.0 g/ml with coefficient of correlation of 0.9998. The limit of detection (LOD) was identifiable and reproducible at 0.102 g/ml and the limit of quantitaion (LOQ) at 0.340 g/ml. This method has ofloxacin recovery was 90.668 0,2635 % for concentration 1.02 g/ml, 92,932 0,6468 % for concentration 3.06 g/ml, and 95,594 3.184 % for concentration 5.1 g/ml."

"ABSTRAKKlopidogrel merupakan obat antiplatelet yang konsentrasinya sangat kecil dalam plasma. Klopidogrel merupakan obat wajib uji bioekivalensi karena merupakan critical use drug yaitu obat yang digunakan pada kondisi serius. Penelitian ini bertujuan untuk melakukan perhitungan kadar klopidogrel dalam plasma subjek sehat sehingga didapatkan profil farmakokinetika klopidogrel. Pada penelitian ini dilakukan analisis klopidogrel secara in vivo dalam plasma tiga subjek sehat secara kromatografi cair kinerja ultra tinggi tandem spektrometri massa KCKUT-SM/SM menggunakan metode yang telah tervalidasi. Sampel plasma diambil setelah subjek diberikan tablet klopidogrel dengan dosis 75 mg sebanyak 14 titik yaitu pada jam ke 0 predose ; 0,25; 0,5; 0,75; 1; 1,25; 1,5; 2; 3; 4; 8; 12; 18; dan 24. Validasi parsial yang dilakukan berupa akurasi dan presisi serta linearitas kurva kalibrasi. Akurasi dan presisi menghasilkan diff dan koefisien variasi KV tidak lebih dari 15 dan tidak lebih dari 20 pada konsentrasi LLOQ. Kurva kalibrasi yang linear didapat pada rentang 20 ndash; 5000 pg/mL. Metode ini telah memenuhi syarat validasi sesuai EMEA Guidelines. Profil farmakokinetika klopidogrel diperoleh berturut-turut sebagai berikut; konsentrasi maksimum Cmax = 1,146 ng/mL; waktu pada konsentrasi maksium tmax = 1 jam; waktu paruh t = 7,01 jam; AUC0-t = 7,420 ng jam/mL; dan AUC0- = 8,111 ng jam/mL.

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ABSTRACTClopidogrel is an antiplatelet drug with a very low plasma concentration. Clopidogrel is a drug that requires bioequivalence test because it is a critical use drug that is used in serious condition. The aim of this study is to perform calculation of clopidogrel concentration in the plasma of healthy subjects to obtain a pharmacokinetics profile of clopidogrel. In this study, clopidogrel analysis was performed in vivo in plasma of three healthy subjects by ultra high performance liquid chromatography ndash tandem mass spectrometry UPLC MS MS using validated methods. Plasma samples were taken after subjects were given clopidogrel tablets with doses of 75 mg at 14 points at 0 predose 0,25 0,5 0,75 1 1,25 1,5 2 3 4 8 12 18 dan 24. Partial validation parameters were intra day accuracy and precicsion and linearity of the calibration curve. Intra day accuracy and precicsion produced diff and coefficient of variation CV not more than 15 and not more than 20 at LLOQ concentration. A linear calibration curve produced in the range of 20 ndash 5.000 pg mL. This method has been fulfilled the criteria for validation accordance to EMEA Guidelines. Pharmacokinetic profile of clopidogrel was obtained respectively as follows maxium concentration Cmax 1.146 ng mL time at maximum concentration tmax 1 hour half life t 7.01 hour AUC0 t 7.420 ng h mL dan AUC0 8.111 ng h mL."

"Esomeprazol adalah obat golongan penghambat pompa proton dengan indikasi untuk refluks gastroesofageal. Esomeprazol tidak stabil terhadap pH, panas, kelembaban dan oksidasi, sehingga seringkali membuat esomeprazol terdegradasi pada saat penyimpanan dan dapat mempengaruhi analisis esomeprazol. Penelitian ini bertujuan untuk menganalisis stabilitas in vivo esomeprazol dalam plasma dengan menguji incurred sample stability esomeprazol pada 6 subjek sehat di hari ke 7, 14 dan 28, pada 2 titik konsentrasi sekitar Cmax dan 1 titik pada fase eliminasi yang sebelumnya ditentukan dengan membuat profil farmakokinetika pada subjek yang diambil sampelnya setelah pemberian esomeprazol magnesium 40 mg. Kondisi kromatografi yang digunakan adalah kolom C18 Waters, SunfireTM 5 um; 250 x 4,6 mm, suhu kolom 40°C fase gerak asetonitril - dapar fosfat pH 7,6 40 : 60 v/v ; laju alir 1,00 mL/menit; detektor photodiode array pada panjang gelombang 300 nm; dan lansoprazol sebagai baku dalam. Profil farmakokinetika esomeprazol dalam sampel plasma memberikan hasil; Cmax 704,57 - 1425,85 ng/mL; tmax rata-rata 2,25 jam; AUC0-t 2444,10 ng.jam/mL. Incurred sample stability esomeprazol pada plasma 6 subjek sehat sampai hari ke-28, menunjukkan hasil yang memenuhi persyaratan berdasarkan EMEA Bioanalytical Guideline tahun 2011 dengan nilai diff tidak lebih dari 20, yaitu 11,64.

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Esomeprazole is one of the proton pump inhibitor that indicated for gastroesophageal reflux. Esomeprazole is unstable against pH, heat, moisture and oxidation, which often makes esomeprazole degraded at the time of storage and may affect the analysis result. This research aims to analyse the in vivo stability of esomeprazole on subjects rsquo plasma samples by testing incurred sample stability of esomeprazole at time of day 7, 14 and 28 on 2 concentration close to Cmax and 1 on the elimination phase after being given 40 mg esomeprazole magnesium. The chromatographic condition was obtained using C18 column Waters, Sunfire trade 5 um 250 x 4.6 mm, column temperature 40°C mobile phase acetonitrile phosphate buffer pH 7.6 40 60 v v a flow rate of 1.00 mL min photodiode array detector at a wavelength of 300 nm and lansoprazole as internal standard. The esomeprazole pharmacokinetics profile in the plasma samples gave results Cmax 704.57 1425.85 ng mL tmax is 2.25 hours AUC0 t 2444 ng.h mL. The result of esomeprazoles incurred sample stability on plasma samples obtained from six healthy subjects until 28 days, shows that it fulfilled the acceptance criteria of EMEA Bioanalytical Guideline with diff value of all incurred samples were less than 20, which is 11.64. "

"The medical benefits of a drug are not only dependent on its biological effect, but also on its "life cycle" within the organism, from its absorption into the blood, distribution to tissue until its eventual breakdown or excretion by the liver and kidneys.Here, the authors, all of them employed at Pfizer in the discovery and development of new active substances, discuss the significant parameters and processes important for the absorption, distribution and retention of drug compounds in the body, plus the potential problems created by their transformation into toxic byproducts. The authors cover everything from the fundamental principles right up to the latest developments using high throughput methods to analyze the pharmacokinetic properties of active substances.Particular emphasis is placed on the impact of pharmacokinetic parameters on the discovery of new drugs, one of the most challenging tasks in global pharmaceutical research."