Simultaneous assay of multiple antibiotics in human plasma by LC–MS/MS: importance of optimizing formic acid concentration

Bioanalysis ◽  
2017 ◽  
Vol 9 (5) ◽  
pp. 469-483 ◽  
Author(s):  
Feng Chen ◽  
Zhe-Yi Hu ◽  
S Casey Laizure ◽  
Joanna Q Hudson
Keyword(s):  
Formic Acid ◽  
Human Plasma ◽  
Acid Concentration ◽  
Multiple Antibiotics

Liquid Chromatography-Tandem Mass Spectrometry Method for Ticagrelor and its Active Metabolite Determination in Human Plasma: Application to a Pharmacokinetic Study

2020 ◽  
Vol 16 (5) ◽  
pp. 602-608
Author(s):  
Niloufar Marsousi ◽  
Serge Rudaz ◽  
Jules A. Desmeules ◽  
Youssef Daali
Keyword(s):  
Clinical Trial ◽  
Formic Acid ◽  
Human Plasma ◽  
Active Metabolite ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Healthy Male ◽  
Coronary Syndrome ◽  
Healthy Male Volunteers ◽  
Male Volunteers

Background: Ticagrelor is a highly recommended new antiplatelet agent for the treatment of patients with acute coronary syndrome at moderate or high ischemic risk. There is a real need for rapid and accurate analytical methods for ticagrelor determination in biological fluids for pharmacokinetic studies. In this study, a sensitive and specific LC-MS method was developed and validated for quantification of ticagrelor and its Active Metabolite (AM) in human plasma over expected clinical concentrations. Methods: Samples were handled by Liquid-Liquid Extraction (LLE). A linear gradient was applied with a mobile phase composed of formic acid 0.1% and acetonitrile with 0.1% of formic acid using a C18 reversed-phase column. MS spectra were obtained by electrospray ionization in negative mode and optimized at 521.4→360.9 m/z, 477.2→361.2 m/z and 528.1→367.9 m/z transitions for ticagrelor, AM and ticagrelor-d7, respectively. Results: This method allowed rapid elution, in less than 4 minutes, and quantification of concentrations as low as 2 ng/mL for ticagrelor and 1 ng/mL for AM using only 100 μL of human plasma. LLE using hexane/ethyl acetate (50/50) was an optimal compromise in terms of extraction recovery and endogenous compounds interference. Trueness values of 87.8% and 89.5% and precisions of 84.1% and 93.8% were obtained for ticagrelor and AM, respectively. Finally, the usefulness of the method was assessed in a clinical trial where a single 180 mg ticagrelor was orally administered to healthy male volunteers. Pharmacokinetic parameters of ticagrelor and its active metabolite were successfully determined. Conclusion: A sensitive and specific quantification LC-MS-MS method was developed and validated for ticagrelor and its active metabolite determination in human plasma. The method was successfully applied to a clinical trial where a single ticagrelor 180 mg dose was orally administered to healthy male volunteers. The described method allows quantification of concentrations as low as 2 ng/mL of ticagrelor and 1 ng/mL of the metabolite using only 100 μL of plasma.

scholarly journals OPTIMASI PRODUKSI PULP FORMACELL DARI TANDAN KOSONG KELAPA SAWIT (TKKS) DENGAN METODE PERMUKAAN RESPON

REAKTOR ◽  
2017 ◽  
Vol 16 (4) ◽  
pp. 161 ◽  
Author(s):  
Sri Hidayati ◽  
Ahmad Sapta Zuidar ◽  
Ahmad Fahreza
Keyword(s):  
Formic Acid ◽  
Acid Concentration ◽  
Oil Palm ◽  
Optimum Concentration ◽  
Optimum Result ◽  
Hcl Concentration ◽  
Pulp Production

ABSTRACT Empty oil-palm bunches (EOPB) contains more enough cellulose so that it can be made as an alternative pulp production.  One of the process of pulp production which friendly environment is by using acetate acid and formic acid called by formacell process.  The aims of the research is to got optimation models of formic acid concentration, HCl concentration and cooking duration for the EFB pulp production.  The optimum result of the EOPB pulp production were 75% of cellulose, 8% of hemiselulosa, 10% of  lignin, and 80% of yield with the optimum concentration 20% of formic acid, 0,5% of HCl, and 2 hour of cooking duration.   Keyword : pulp formacell, EFB, RSM.   ABSTRAK Tandan kosong kelapa sawit (TKKS) mengandung kadar selulosa yang cukup tinggi sehingga dapat dijadikan sebagai bahan baku alternatif produksi pulp.  Salah satu proses produksi pulp ramah lingkungan yaitu dengan menggunakan campuran pelarut asam asetat dan asam formiat sebagai bahan pemasak yang disebut proses formacell.  Tujuan dari penelitian ini untuk mendapatkan model optimasi dari konsentrasi asam formiat, konsentrasi HCl dan lama pemasakan untuk produksi pulp TKKS.  Konsentrasi pemasakan optimum terjadi pada konsentrasi asam formiat 20%, konsentrasi HCl 0,5%, dan lama pemasakan selama 2 jam dengan hasil optimum untuk produksi pulp TKKS yaitu 75 % selulosa, 8 % hemiselulosa, 10% lignin, dan 80% rendemen.   Kata kunci: pulp formacell, TKKS, RSM.    

scholarly journals DEVELOPMENT AND VALIDATION OF LC-MS/MS METHOD FOR ESTIMATION OF UROCARB IN HUMAN PLASMA

2019 ◽  
pp. 125-130
Author(s):  
IRYNA DRAPAK ◽  
BORYS ZIMENKOVSKY ◽  
LINA PEREKHODA ◽  
SERGIY KOVALENKO ◽  
LILIYA LOGOYDA
Keyword(s):  
Formic Acid ◽  
Human Plasma ◽  
Internal Standard ◽  
Sample Volume ◽  
Pharmacokinetic Studies ◽  
Coefficients Of Variation ◽  
Highly Sensitive ◽  
Regulatory Guidelines ◽  
Initial Content ◽  
Development And Validation

Objective: The present study was aimed to develop a rapid, specific and sensitive method based on LC-MS/MS method was developed for the determination of urocarb using etomidate as an internal standard. Methods: Chromatography was achieved on Discovery C18, 50 × 2.1 mm, 5 μm column. Samples were chromatographed in a gradient mode (eluent A (acetonitrile-water–formic acid, 5: 95: 0.1 v/v), eluent B (acetonitrile–formic acid, 100: 0.1 v/v)). The initial content of the eluent B of 8%, which increases linearly to 1.0 min to 100%, is maintained up to 1.5 min and returned to the original 8% to 1.51 min. The mobile phase was delivered at a flow rate of 0.400 ml/min into the mass spectrometer ESI chamber. The sample volume was 4 μl. Results: The total chromatographic run time was 2.0 min and the elution of urocarb and IS (etomidate) occurred at ~1.53 and 1.67 min, respectively. A linear response function was established at 1-100 ng/ml for urocarb and etomidate in human plasma. The % mean recovery for urocarb in LQC, MQC and HQC was 104.1 %, 100.0 % and 97.4 %. The lowest concentration with the RSD<20% was taken as LLOQ and was found to be 1.03 ng/ml for urocarb. The within-run coefficients of variation ranged between 0.271 % and 0.478 % for urocarb. The within-run percentages of nominal concentrations ranged between 99.12 % and 100.21 % for urocarb. The between-run coefficients of variation ranged between 0.388 % and 0.601 % for urocarb. The between-run percentages of nominal concentrations ranged between 98.78 % and 101.11 % for urocarb. Conclusion: A highly sensitive, specific, reproducible, rapid and high-throughput LC-MS/MS assay was developed and validated to quantify urocarb in human plasma as per the regulatory guidelines. Due to the sensitivity of the developed method, it can be applied to the monitoring of plasma levels in the analysis of drug in preclinical and clinical pharmacokinetic studies. All the parameters and results were found within the acceptance limit as given in the validation protocol.

scholarly journals LC-MS/MS METHOD DEVELOPMENT AND VALIDATION FOR THE DETERMINATION OF CARDIAZOL IN HUMAN PLASMA

2019 ◽  
pp. 380-385
Author(s):  
IRYNA DRAPAK ◽  
BORYS ZIMENKOVSKY ◽  
LINA PEREKHODA ◽  
SERGIY KOVALENKO ◽  
Liliya Logoyda
Keyword(s):  
Formic Acid ◽  
Human Plasma ◽  
Method Development ◽  
Accurate Method ◽  
Sample Volume ◽  
Ich Guidelines ◽  
Coefficients Of Variation ◽  
Method Development And Validation ◽  
Development And Validation

Objective: The main purpose of this study was to develop a simple, precise, rapid and accurate method for the quantification of cardiazol in human plasma. Methods: Chromatography was achieved on Discovery C18, 50 × 2.1 mm, 5 μm column. Samples were chromatographed in a gradient mode (eluent A (acetonitrile-water–formic acid, 5: 95: 0.1 v/v), eluent B (acetonitrile–formic acid, 100: 0.1 v/v)). The initial content of the eluent B of 8%, which increases linearly to 1.0 min to 100%, is maintained up to 1.5 min and returned to the original 8% to 1.51 min. The mobile phase was delivered at a flow rate of 0.400 ml/min into the mass spectrometer ESI chamber. The sample volume was 300 μl. Results: The total chromatographic run time was 2.5 min and the elution of cardiazol and IS (difenoconazole) occurred at ~2.15 and 1.98 min, respectively. A linear response function was established at 1-100 ng/ml for cardiazol and difenoconazole in human plasma. The % mean recovery for cardiazol in LQC, MQC and HQC was 102.8 %, 100.3 % and 95.9 %. The lowest concentration with the RSD<20% was taken as LLOQ and was found to be 1.10 ng/ml for cardiazol. The % accuracy of LLOQ samples prepared with the different biological matrix lots was found 109.7 %, which were found within the range of 80.00-120.00 % for the seven different plasma lots. % CV for LLOQ samples was observed as 11.9 %, which are within 20.00% of the acceptance criteria. The within-run coefficients of variation ranged between 0.311 % and 0.601 % for cardiazol. The within-run percentages of nominal concentrations ranged between 99.80 % and 100.41 % for cardiazol. The between-run coefficients of variation ranged between 0.332 % and 0.615 % for cardiazol. The between-run percentages of nominal concentrations ranged between 98.18 % and 101.21 % for cardiazol. Conclusion: A rapid method was developed for simultaneous determination of cardiazol in human plasma. The method was strictly validated according to the ICH guidelines. Acquired results demonstrate that the proposed strategy can be effortlessly and advantageously applied for routine examination of cardiazol in human plasma.

scholarly journals Formic Acid Pulping of Bagasse

1970 ◽  
Vol 41 (3) ◽  
pp. 245-250 ◽  
Author(s):  
M Sarwar Jahan
Keyword(s):  
Formic Acid ◽  
Acid Concentration ◽  
Strength Properties ◽  
Kappa Number ◽  
Cooking Time ◽  
Pulp Yield ◽  
Cooking Conditions

Atmospheric formic acid pulping of bagasse was done with varying formic acid concentration and cooking time. Pulp yield and kappa number decreased with increasing formic acid concentration or cooking time. The optimal cooking conditions were 90 % formic acid and 90 min of cooking at 95°C. The pulp yield at this condition was 44.4 % and kappa number 26.1. The strength properties were acceptable in formic acid pulping of bagasse. Addition of H2SO4 catalyst in formic acid degraded carbohydrate, resulting lower pulp yield and inferior strength properties. The strength properties were improved slightly after bleaching. Bangladesh J. Sci. Ind. Res. 41(3-4), 245-250, 2006

scholarly journals Bioanalytical method development and validation for the determination of metoprolol and meldonium in human plasma

Pharmacia ◽  
2020 ◽  
Vol 67 (2) ◽  
pp. 39-48
Author(s):  
Mariana Horyn ◽  
Liliya Logoyda
Keyword(s):  
Formic Acid ◽  
Human Plasma ◽  
Mobile Phase ◽  
Method Development ◽  
Accurate Method ◽  
Ich Guidelines ◽  
Method Development And Validation ◽  
Phase Water ◽  
Development And Validation

Aim.The main purpose of this study was to develop a simple, precise, rapid and accurate method for the quantification of metoprolol and meldonium in human plasma. Materials and methods. The resolution of peaks of metoprolol was best achieved with Discovery C18, 50 × 2.1 mm, 5 μm column and meldonium - ZORBAX HILIC Plus, 50 × 2.1 mm, 3.5 μm column. Samples of metoprolol were chromatographed in a gradient mode (eluent A (acetonitrile – water – formic acid, 5 : 95 : 0.1 v/v), eluent B (acetonitrile – formic acid, 100 : 0.1 v/v)). The initial content of the eluent B is 0%, which increases linearly by 1.0 min to 100% and to 1.11 min returns to the initial 0%. The mobile phase was delivered at a flow rate of 0.400 mL/min into the mass spectrometer ESI chamber. The injection volume was 5μl. Samples of meldonium were chromatographed in a isocratic using mobile phase water – acetonitrile – ammonium formate buffer 200 мМ, 20 : 75 : 5 v/v). Results.The total chromatographic run time was 2.0 minutes and the elution of metoprolol, meldonium and IS occurred at ~1.39 and 1.18 minutes, respectively.A linear response function was established at 2 - 200 ng/mL for metoprolol and 50 -5000 ng/mL for meldonium in human plasma. The% mean recovery for metoprolol in LQC, MQC and HQC was 99.0%, 107.5% and 96.8%, for meldonium in LQC, MQC and HQC was 94.1%, 100.2% and 93.1% respectively. The lowest concentration with the RSD &lt;20% was taken as LLOQ and was found to be 2.31 ng/mL for metoprolol, 47.70 ng/mL for meldonium. The % accuracy of LLOQ samples prepared with the different biological matrix lots were found 115.4% for metoprolol and 95.5% for meldonium, which were found within the range of 80.00–120.00% for the seven different plasma lots. % CV for LLOQ samples was observed as 12.8% and 7.7% respectively, which are within 20.00% of the acceptance criteria. Conclusion.A rapid method was developed for simultaneous determination of metoprolol and meldonium in human plasma. The method was strictly validated according to the ICH guidelines. Acquired results demonstrate that proposed strategy can be effortlessly and advantageously applied for routine examination of metoprolol and meldonium in human plasma.

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