A high-performance thin-layer chromatography method was developed for the simultaneous quantitative determination of diclofenac sodium and benzyl alcohol and employed for the assay of these analytes in pharmaceutical injection solutions. The method used a silica gel 60 F254 plate and a mixture of n‑hexane–chloroform–acetone–acetic acid (60 : 60 : 35 : 0.75, v/v/v/v) as the mobile phase for chromatographic separation of the analytes. The samples were applied on the thin-layer plate as 4-mm-wide bands with a band-to-band distance of 9 mm; the distance from the bands to the bottom of the plate was 1 cm, and the development distance was 85 mm. The applied sample volume was 6.0 μL. After plate development, the chromatograms were scanned at 210 nm to detect analytes and to calculate their peak areas. The method was validated according to the guidelines of the International Council for Harmonization and Association of Official Analytical Collaboration International in terms of system suitability, specificity, linearity, accuracy, precision, and robustness. The validation results confirmed that the method was suitable and reliable for the intended purpose and was applied for the quality control of commercial products.

A validated instrumental thin-layer chromatography (TLC) method was developed and applied for the simultaneous quantitation of esomeprazole and naproxen in fixed-dose combination pharmaceutical tablets. The method employed a silica gel plate and a mixture of chloroform–ethyl acetate–methanol–glacial acetic acid (3:7:1:0.2, V/V) as the mobile phase. Samples were applied on plate as 6-mm long bands. The band-to-band distance was 9 mm. The distance between the bands and the bottom of the plate was 8 mm. The applied volume was 7.0 µL/band. The developing distance was 85 mm. After development, the plates were scanned at 302 nm to detect spots and to record chromatograms. The method was proved to be accurate (overall recovery ranges were from 97.7

A green, cost-effective Raman spectroscopic method for assay of cefuroxime axetil in tablets was developed using powdered paracetamol as matrix modifier. The Raman spectra were preprocessed by Standard Normal Variate, Savitzky-Golay 1st Differential and Centering, and preprocessed spectral data at Raman shift zones from 765 to 910 cm−1, 1300 to 1430 cm−1, 1440 to 1515 cm−1, and 1560 to 1675 cm−1 were extracted to establish assay model using Partial Least Square regression with 5 factors. The method was fully validated according to requirements of ICH and AOAC International on the range of αM (the ratio, calculated in % (w/w), between the mass of cefuroxim axetil and the total mass of cefuroxim axetil and matrix modifier in test mixture) from 35% to 65%. Within this range, the method was accurate (average recoveries were 100.2% (n = 6, RSD = 0.7%) at αM = 35%, 99.4% (n = 6, RSD = 1.0%) at αM = 50%, and 99.5% (n = 6, RSD = 1.1%) at αM = 65%) and precise (repeatability studies in two separate days gave RSD values at 1.0% and 1.4%, respectively, and RSD for intermediate precision was 1.1%). The method was also robust against ±20% variations in mass content of some excipients (average recoveries from 98.7% to 99.9%, RSD values from 0.3% to 0.8%) and ±5% variations in mass content cefuroxime axetil in samples (average recoveries from 99.1% to 99.9%, RSD values from 0.4% to 1.1%). The greenness score of the method, estimated with Agree application on 12 criteria, was 0.72.

Octylmethoxycinnamate (OMC), octylsalicylate (OS) are UV filters commonly used in sunscreen creams for skin protection against UV radiations. In this study, an HPTLC method was developed and validated for simultaneous determination of OMC and OS in sunscreen creams. The method was carried out using an silica gel 60 F254 thin layer plate (20 cm × 10 cm) with a mixture of cyclohexane - aceton (10:1, v/v) as mobile phase. Samples were applied on thin layer plate as 4-mm bands with applied volume at 7.0 µL per band and the distance between two consecutive bands was 9 mm. The chromatograms were developed over a distance of 80mm, then scanned and recorded at 307 nm for peak detection and calculation of peak area. The method was fully validated according to requirements on analytical method performance of AOAC International. The linearity ranges of the method were from 17.9 to 32.2 µg/mL for OMC and from 16.3 to 29.4 µg/mL for OS, respectively, and its accuracy (recovery rate from 97.4% to 102.2% for OMC and from 98.0% to 102.4% for OS) and its precision (RSD ≤ 2.6% for OMC and ≤ 2.4 % for OS) were sufficient for simultaneous determination of these two UV filters. Therefore, validation results confirmed its reliability and suitability for intended application. The method was employed to determine the content of OMC and OS in commercial sunscreen creams. Keywords: HPTLC, UV filter, sunscreen cream, octyl methoxycinnamate, octyl salicylate

Salicylic acid (SA), sodium benzoate (SB), phenoxyethanol (PO), and benzyl alcohol (BA) are “non paraben” preservatives commonly used in cosmetic products like shampoos, and often in combination of at least two compounds to assure their antimicrobial effectiveness at low concentrations. In this study, an HPLC-DAD method was developed and validated for simultaneous determination of SA, SB, PO, and BA in commercial shampoos. The method was carried out using an YMC Triart C18 (250 × 4.6 mm, 5 µm) column with a mixture of methanol and 0.02 M solution of phosphate buffer pH 2.7 (35 : 65, v/v) as mobile phase. The flow rate of mobile phase was maintained at 1.0 mL per minute, the injection volume was 20 µL and the UV detection was done at 208 nm for BA and at 230 nm for SA, SB and PO. The method was fully validated according to requirements on analytical method performance of AOAC International and validation results confirmed its reliability and suitability for intended application. The method was employed to determine the four “non paraben” preservatives in 18 commercial shampoos, finding the actual content of these substances in all samples conformed to their regulatory limits.

[This corrects the article DOI: 10.1016/j.heliyon.2023.e14647.].

The ATR-FTIR quantitation of azithromycin in three products of commercial tablets was carried out on product specific quantitative regression models using powdered paracetamol as matrix modifier to overcome the variation of spectral response and influence of sample matrix. For each product, a PLS quantitative regression model was established using training infrared spectra obtained from reference mixtures (reference powders with known mass content (%, w/w) of azithromycin mixed homogenously with paracetamol to have mass percentage of azithromycin over total mass of azithromycin and paracetamol (PA) from 30% to 70%). The spectral data were collected in wavenumber range depending on commercial product within the wavenumber zone from 1300 cm-1 to 1750 cm-1 to build quantitative regression models. To quantify azithromycin in any commercial batch of the same product, the homogenized sample powder was mixed with paracetamol to have mixtures with PA value about 50% to record infrared spectrum. The actual amount of azithromycin would then be calculated from spectral response of unknown sample and the pre-established quantitative regression model. Each quantitative regression model was validated according to the current requirements of ICH guideline Q2R1 and those of AOAC International in term of specificity, accuracy, precision, long-term robustness and reliability. The validation results proved that the quantitative regression models were accurate, precise, reliable and robust, able to provide quantitative results of azithromycin in tablets equivalent to those provided by official HPLC method of USP44.

Vitamins and minerals are usually incorporated in pharmaceutical and nutraceutical products, but a simple, rapid, and inexpensive analytical method for their simultaneous determination is still lacking. In this study, we developed a quantification method for pyridoxine (vitamin B6) and magnesium (Mg) by using purpose-made capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) instrument. Main analytical conditions include: fused silica capillary (total length 55 cm, effective length 40 cm, inner diameter 50 mu m); background electrolyte consisted of 10 mM L-arginine/acetic acid (pH 5) with 20% acetonitrile; separation voltage + 20 kV; hydrodynamic injection (siphoning at 20 cm in 25 s). Detection limits of vitamin B6 and Mg were 1 and 0.1 mg/L, respectively. Good linearity (R2 > 0.999) was observed for vitamin B6 and Mg calibration curves over concentration ranges of 3-100 and 0.3-200 mg/L, respectively. The method was applied to analyze vitamin B6 and Mg in several pharmaceutical and nutraceutical samples. The analytical results obtained by our method were in good agreement with reference methods (i.e., HPLC for vitamin B6 and ICP-OES for Mg). High-efficient and low-cost CE-C4D method can accordingly serve as a promising tool for concurrent analysis of inorganic and organic species in pharmaceutical and nutraceutical analysis.

A green, cost-effective, and simple capillary zone electrophoresis (CZE) method was developed and validated for simultaneous determination of chloramphenicol, methylparaben, and propylparaben in eye-drops. With sodium tetraborate as background electrolyte (BGE), the apparent mobilities of chloramphenicol, methylparaben, and propylparaben increased and analysis time reduced when pH of BGE increased from 8.5 to 10.0 and concentration of BGE decreased from 40 mM to 15 mM, but complete separation of chloramphenicol from other matrix components was achieved only with sodium tetraborate concentration at 30 mM or higher and at pH = 9.3 or lower. The most suitable electrophoretic conditions for the intended application were a 30 mM sodium tetraborate solution, pH 9.3 as BGE, working voltage set at 25 kV, and UV detection at 280 nm at the cathodic extremity of the capillary. The final method was validated and proved to be reliable for assay of chloramphenicol, methylparaben, and propylparaben in eye-drops.

A simple, easy-to-implement, and green infrared spectroscopic method was developed and validated for the quantitative determination of sildenafil citrate in tablets of unknown manufacturing formula. Homogenized tablet powder with known mass content (%, m/m) of sildenafil citrate was mixed with paracetamol to form standard mixtures with different percentages of sildenafil citrate on the total quantity of sildenafil citrate and paracetamol (designated as R). Unknown tablet samples were finely ground and mixed with paracetamol to form test mixtures having R values about 50%. Infrared spectra of standard mixtures, measured in attenuated total reflectance mode, in the wavenumber zone from 1800 cm−1 to 1300 cm−1 were selected and processed by partial least square regression to form the calibration model for quantitation of sildenafil citrate in unknown samples. Spectral responses of test mixtures and the calibration model were used to determine the exact mass content (%, m/m) of sildenafil citrate in the powder of unknown tablet samples. The method was fully validated in terms of linearity, precision, and accuracy according to the requirements of current guidelines and was proved as reliable and suitable for the intended application.

A green, cost-effective, and simple capillary zone electrophoresis (CZE) method was developed and validated for simultaneous determination of chloramphenicol, methylparaben, and propylparaben in eye-drops. With sodium tetraborate as background electrolyte (BGE), the apparent mobilities of chloramphenicol, methylparaben, and propylparaben increased and analysis time reduced when pH of BGE increased from 8.5 to 10.0 and concentration of BGE decreased from 40mM to 15mM, but complete separation of chloramphenicol from other matrix components was achieved only with sodium tetraborate concentration at 30mMor higher and at pH� 9.3 or lower.(emost suitable electrophoretic conditions for the intended application were a 30mM sodium tetraborate solution, pH 9.3 as BGE, working voltage set at 25 kV, and UV detection at 280 nm at the cathodic extremity of the capillary. (e final method was validated and proved to be reliable for assay of chloramphenicol, methylparaben, and propylparaben in eye-drops.

Background: Ceftazidime and imipenem have been increasingly used to treat Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) due to their extended-spectrum covering Pseudomonas aeruginosa. This study aims to describe the population pharmacokinetic (PK) and pharmacodynamic (PD) target attainment for ceftazidime and imipenem in patients with AECOPD. Methods: We conducted a prospective PK study at Bach Mai Hospital (Viet Nam). A total of 50 (ceftazidime) and 44 (imipenem) patients with AECOPD were enrolled. Population PK analysis was performed using Monolix 2019R1 and Monte Carlo simulations were conducted to determine the optimal dose regimen with respect to the attainment of 60% and 40% fT>MIC for ceftazidime and imipenem, respectively. A dosing algorithm was developed to identify optimal treatment doses. Results: Ceftazidime and imipenem PK was best described by a one-compartment population model with a volume of distribution and clearance of 23.7 L and 8.74 L/h for ceftazidime and 15.1 L and 7.88 L/h for imipenem, respectively. Cockcroft–Gault creatinine clearance represented a significant covariate affecting the clearance of both drugs. Increased doses with prolonged infusion were found to cover pathogens with reduced susceptibility. Conclusions: This study describes a novel and versatile three-level dosing algorithm based on patients’ renal function and characteristic of the infective pathogen to explore ceftazidime and imipenem optimal regimen for AECOPD.

A dietary exposure and health risk assessment of mycotoxins including aflatoxin B1, fumonisin B1, ochratoxin A, and zearalenone was conducted in 3 provinces in Northern Vietnam namely Hanoi, Thanh Hoa, and Ha Giang. Results of the analysis of samples of maize, rice, peanut, and sesame revealed the presence of these mycotoxins in all samples and sampling locations. Aflatoxin B1 was the most frequently detected (19.1%) and widely distributed among different types of samples, whereas the percentage occurrence of fumonisin B1, ochratoxin A, and zearalenone were 11.2, 5.9 and 6.3, respectively. The later three mycotoxins were detected mostly in maize. The exposure to aflatoxin B1 at detected levels could lead to 0.23, 0.65 and 21.0 cases of liver cancer per 100,000 adult people per year in Hanoi, Thanh Hoa and Ha Giang, respectively. The risk assessment also showed the unsafe exposure to ochratoxin A and fumonisin B1 in the highland region where the people consume a large amount of foods derived from maize. In Ha Giang, the mean exposures to fumonisin B1 were lower than its PMTDI (Provisional Maximum Tolerable Daily Intake), however, the 95th percentile values were 1.1–1.9 times of the PMTDI. The mean exposures to ochratoxin A in Ha Giang were about 2.4–3.6 times higher than its PMTWI (Provisional Maximum Tolerable Weekly Intake). There was no risk of fumonisin B1 and ochratoxin A in Hanoi and Thanh Hoa. The dietary exposure to zearalenone was within its PMTDI in all locations. The results pointed out the need for further improvement of the control of these mycotoxins in Vietnam, especially in some highland provinces.

(Ngày đến tòa soạn: 15/01/2020; Ngày sửa bài sau phản biện: 15/02/2020; Ngày chấp nhận đăng: 20/03/2020) Tóm tắt Phương pháp sắc ký lỏng khối phổ hai lần (LC­MS/MS) đã được áp dụng để nghiên cứu xác định đồng thời 04 độc tố vi nấm nhóm ergot alkaloids (EAs) bao gồm: ergosine, ergocryptine, ergocristine, ergocorsine trong thực phẩm. Các độc tố vi nấm EAs trong thực phẩm được chiết, làm sạch bằng kỹ thuật QuEChERS và được tách bằng sắc ký lỏng với cột C18 và định lượng bằng detector khối phổ ba tứ cực. Nguồn ion hóa ESI (+), chế độ theo dõi ion MRM đã được sử dụng trong nghiên cứu. Giá trị sử dụng của phương pháp được xác nhận theo hướng dẫn của AOAC. Kết quả cho thấy phương pháp có tính đặc hiệu tốt, đường chuẩn được xây dựng trong khoảng nồng độ từ 5,0 ­ 100 μg/kg, giới hạn phát hiện 0,3 μg/kg, giới hạn định lượng 1,0 μg/kg; độ chụm và độ đúng với hệ số biến thiên lặp lại RSD < 12,5% và độ thu hồi dao động từ 90,6 ­ 102,8%, đáp ứng yêu cầu theo AOAC. Phương pháp được áp dụng để đánh giá hàm lượng các độc tố vi nấm EAs trong một số sản phẩm thực phẩm như: ngô, lúa mỳ và bột ngũ cốc dinh dưỡng; chưa phát hiện thấy độc tố nhóm EAs trong các mẫu phân tích. Từ khóa: ergot alkaloids, ergosine, ergocryptine, ergocristine, ergocorsine, LC­MS/MS, lúa mỳ, ngô, ngũ cốc. 1. ĐẶT VẤN ĐỀ Egot alkaloids (EAs) là độc tố vi nấm có nguồn gốc từ tryptophan được sinh ra bởi các loại nấm khác nhau, đặc biệt là các loài Claviceps spp. trong đó phổ biến nhất là Claviceps purpureas [1]. Nấm phát triển trong giai đoạn ra hoa, xâm chiếm noãn, sử dụng dinh dưỡng của cây chủ, hình thành hạch nấm có lớp tế bào cứng, sẫm màu, hình lưỡi liềm và thay thế nhân hạt sau 3 ­ 4 tuần xâm nhiễm. Hạch nấm của loài Claviceps spp. được gọi là sclerotia hay ergot [1], [2]. EAs tồn tại trong hạt và khó loại bỏ được bằng các cách sàng lọc thông thường. Các độc tố này thường xuất hiện trong các loại ngũ cốc như lúa mạch, lúa mì, lúa mạch đen, yến mạch và một số loại ngũ cốc khác. Trên thế giới đã có nhiều nghiên cứu xác định hàm lượng EAs trong lúa mì, lúa mạch và sản phẩm ngũ cốc,... [3 ­ 6]. Hiện nay, một số nước châu Âu đã đưa ra ngưỡng quy định về EAs trong các sản phẩm thực phẩm, theo đó các phương pháp phân tích cần phải đạt ngưỡng giới hạn định lượng được tối thiểu là 1,0 μg/kg. Phương pháp LC­MS/MS kết hợp xử lí mẫu bằng kỹ thuật QuEChERS có nhiều ưu điểm vượt trội như độ nhạy tốt, độ đặc hiệu cao, thời gian phân tích nhanh, có thể phân tích đồng thời, quá trình xử lý mẫu đơn giản, đã được nhiều tác giả nghiên cứu để xác định EAs trong các nền mẫu. Tuy nhiên, xử lý mẫu theo QuEChERS đòi hỏi cần phải khảo sát loại pha rắn phù hợp cho các nền mẫu khác nhau, để có thể loại trừ ảnh hưởng

A sensitive GC-MS/MS method has been developed and validated for determining ester forms of 3-MCPD and 2-MCPD in infant formula, using 3-MCPD-d5 and 2-MCPD-d5 as internal standards, respectively. The esters of MCPDs were extracted from infant formula powder with mixture of ethanol/n-hexane/diethyl ether (1/1/1, v/v/v), then treated with sulfuric acid to release free MCPDs. Free MCPDs and internal standards were derivatized with phenylboronic acid and the corresponding derivatives were used for GC-MS/MS analysis. The chromatographic separation was performed in a DB-5MS capillary column using helium as mobile phase at flow rate of 1 mL/min. Tandem mass spectroscopic detection of each analyte was done in MRM mode by monitoring one precursor ion and two product ions. Validation results confirmed the suitability of the developed method for intended application. Application of the method in samples collected from different provinces in Vietnam detected esterified 3-MCPD in 38.9% of samples, esterified 2-MCPD in 34.7% of samples.

A simple and accurate LC-MS/MS method has been developed for the simultaneous determination of four ergot alkaloids (EAs) including ergosine, ergocryptine, ergocristine and ergocorsine in food. The studied EAs were extracted and cleaned up using QuEChERS technique then separated using C18 column and quantified by MS/MS detector. The positive ESI source was used in this study together with multi-reactive ion monitoring mode. The method, which has been validated according to AOAC International requirements, showed good specificity, with the linearity varying from 5.0 µg/kg to 100 µg/kg, the LODs and LOQs were 0.3 µg/kg and 1.0 µg/kg; the repeatability and recovery were from 3.7 to 12.5 % and 90.6 - 102.8% respectively. The method has been applied to determine the EAs concentration in 90 corn, wheat and cereal samples, of which no samples were detected with the studied EAs.

The aim of the present study was the development and validation of a simple, precise and specific reversed phase HPLC method for the simultaneous determination of coumarin, cinnamyl alcohol, cinnamaldehyd, acid cinnamic, eugenol, cinnamyl acetat, acid 2-hydroxycinnamic in cinnamon. The substances were extracted from the sample matrix with methanol, shaken at room temperature for 30 minutes and determined by HPLC-PDA on the following conditions: column C18 sunfire (250 × 4.6 mm, 5 µm), mobile phase 30mM ammonium acetate and methanol-acetonitrile (50:50) using gradient. The recovery > 90%, the repeatability has RSD < 7.3%, the LODs and LOQs of2-hydroxycinnamic acid, coumarin, cinnamaldehyd, cinnamyl alcohol, eugenol were 1 µg/g and 3.3 µg/g, respectively; the LODs and LOQs of cinnamic acid, cinnamyl acetate were 2 µg/g and 6.7 µg/g, respectively. The method has been applied to analyze the samples.

Việc lạm dụng các chất tăng trưởng thực vật trong nông nghiệp, đặc biệt là các chất có nguồn gốc tổng hợp nhóm cytokinin, có xu hướng ngày càng gia tăng. Trong nghiên cứu này, phương pháp xác định hai chất tăng trưởng thực vật nhóm cytokinin gồm 6-benzylaminopurine và forchlorfenuron trong giá đỗ đã được nghiên cứu xây dựng dựa trên kỹ thuật chiết QuEChERS kết hợp với LC-MS/MS. Điều kiện sắc ký gồm cột pha đảo C18, pha động ở chế độ gradient với hai kênh H2O và MeOH có bổ sung thêm hỗn hợp acid formic 0,1% và amoni formate 10 mM. Detector khối phổ ba tứ cực, với nguồn ion hóa phu điện tử dương (ESI+), chế độ theo dõi đa phản ứng (MRM) đã được sử dụng để khẳng định sự có mặt của các chất nghiên cứu. Quy trình xử lý mẫu được tối ưu theo phương pháp QuEChERS sử dụng ACN làm dung môi chiết, PSA làm chất hấp phụ cho hiệu quả chiết tốt. Phương pháp xây dựng có LOQ đạt 3,0 µg/kg với độ thu hồi từ 79,1% đến 117%, độ lặp lại từ 3,0% đến 7,0% đạt yêu cầu theo quy định của AOAC và Châu Âu. Phương pháp đã được ứng dụng để phân tích một số mẫu giá đỗ trên địa bàn thành phố Hà Nội, có 5/6 mẫu được phát hiện có 6-benzylaminopurine với hàm lượng vượt giới hạn tồn dư tối đa theo quy định châu Âu.

In this study, the development of our purpose-made capacitively coupled contactless conductivity detection ((CD)-D-4) for CE is reported. These systems have been employed as a simple, versatile, and cost-effective analytical tool. CE-(CD)-D-4 devices, whose principle is based on the control of the ion movements under an electrical field, can be constructed even with a modest financial budget and limited infrastructure. A featured application was developed for quality control of antimicrobial drugs using CE-(CD)-D-4, with most recent work on determination of aminoglycoside and glycopeptide antibiotics being communicated. For aminoglycosides, the development of CE-(CD)-D-4 methods was adapted to two categories. The first one includes drugs (liquid or powder form) for intravenous injection, containing either amikacin, streptomycin, kanamycin A, or kanamycin B. The second one covers drugs for eye drops (liquid or ointment form), containing either neomycin, tobramycin, or polymyxin. The CE-(CD)-D-4 method development was also made for determination of some popular glycopeptide antibiotics in Vietnam, including vancomycin and teicoplanin. The best detection limit achieved using the developed CE-(CD)-D-4 methods was 0.5 mg/L. Good agreement between results from CE-(CD)-D-4 and the confirmation method (HPLC- Photometric Diode Array ) was achieved, with their result deviations less than 8% and 13% for aminoglycoside and glycopeptide antibiotics, respectively.

Nghiên cứu đã phát triển và thẩm định phương pháp xác định đồng thời các dạng ester của 3-MCPD và 2-MCPD trong sữa công thức bằng GC-MS/MS. Các ester của MCPD được chiết từ mẫu sữa công thức bằng hỗn hợp ethanol/n-hexane/diethyl ether (1/1/1, v/v/v), sau đó được xử lý với acid sulfuric để giải phóng dạng tự do. Các chất 3-MCPD và 2-MCPD dạng tự do và nội chuẩn đồng vị 3-MCPD-d5 and 2-MCPD-d5 được dẫn xuất với acid phenylboronic và sau đó dẫn xuất được phân tích bằng GC-MS/MS ở chế độ MRM. Cột tách được sử dụng là cột mao quản DB-5MS, khí mang là Heli ở tốc độ 1 mL/phút. Chế độ MRM đã được sử dụng để lựa chọn 1 ion mẹ và 2 ion con cho mỗi chất phân tích. Kết quả thẩm định cho thấy phương pháp đáp ứng các yêu cầu theo AOAC SMPR. Phương pháp đã được ứng dụng để xác định các ester của 3-MCPD và 2-MCPD trong các mẫu sữa công thức lấy ở một số tỉnh, thành phố của Việt Nam. Có 38,9% số mẫu phát hiện 3-MCPD ester và 34,7% số mẫu phát hiện 2-MCPD ester.