Formulation and Stability of a 1% Clarithromycin-Based Topical Skin Cream: A New Option to Treat Buruli Ulcers?

There are more than 170 known species of non-tuberculous mycobacteria, and some are responsible for serious diseases in people infected with them. One of these is Buruli ulcers, a neglected tropical disease endemic in more than 33 countries and caused by Mycobacterium ulcerans, which infects skin tissue. Treatment consists of a long-term regimen combining the use of oral rifampin with another anti-tuberculosis drug (e.g., clarithromycin). Patients in these countries face difficulties in accessing and adhering to this therapy. This study investigates the feasibility of formulating stable, optimized clarithromycin as a topical cutaneous cream. The cream was formulated, and its stability was evaluated under different storage temperature conditions and using a stability indicator method. The results showed that the clarithromycin cream was stable for at least 60 days, even at extreme temperatures (40 °C). In conclusion, the data presented here demonstrate the stability of a new form of topical cutaneous clarithromycin, which may offer a new approach to the treatment of Buruli ulcers and clarithromycin-sensitive infections.

Physical compatibility of ceftriaxone and cefepime in 0.45% sodium chloride, Ringer's lactate solution, and Plasma-Lyte A.

OBJECTIVES: The compatibility of intravenous fluids with medications is of paramount concern to pharmacists and is an imperative component of ensuring patient safety. Data regarding the physical compatibility of medications with intravenous fluids has not been examined, or published with conflicting results or the concentrations studied were not consistent with current practice. Our objective was to determine the physical compatibility of ceftriaxone and cefepime in 0.45% sodium chloride, Ringer's lactate solution, and Plasma-Lyte A. METHODS: An in vitro analysis of the physical compatibility of ceftriaxone and cefepime at 10 mg/mL, 20 mg/mL, and 40 mg/mL concentrations was conducted in 0.45% sodium chloride, Ringer's lactate solution, and Plasma-Lyte A. Admixtures were evaluated in triplicate at hours 0, 1, 5, 8, and 24. Physical compatibility was assessed by visual inspection, spectrophotometry, and pH analysis. RESULTS: Ceftriaxone 40 mg/mL was found to be physically incompatible in 0.45% sodium chloride and Ringer's lactate solution beyond 5 hours and in Plasma-Lyte A beyond 8 hours. Cefepime was found to be physically incompatible with all fluids and in all concentrations beyond 1 hour. CONCLUSIONS: This work contributes to the body of literature dedicated to the evaluation of intravenous drug and fluid physical compatibility by identifying demonstrable changes in admixtures containing 0.45% sodium chloride, Plasma-Lyte A, and Ringer's lactate solution. Ceftriaxone should not be administered with 0.45% sodium chloride, Ringer's lactated solution, or Plasma-Lyte A at selected concentrations and time points and cefepime is not considered to be physically compatible at 10 mg/mL, 20 mg/mL, or 40 mg/mL in any of the studied fluids beyond 1 hour.

[Translated article] Implementation of a traceability and safe drug preparation system in a clean room.

OBJECTIVE: To describe the process of implementing a traceability and safe manufacturing system in the clean room of a pharmacy service to increase patient safety, in accordance with current legislation. METHODS: The process was carried out between September 2021 and July 2022. The software program integrated all the recommended stages of the manufacturing process outlined in the "Good Practices Guide for Medication Preparation in Pharmacy Services" (GBPP). The following sections were parameterised in the software program: personnel, facilities, equipment, starting materials, packaging materials, standardised work procedures, and quality controls. RESULTS: A total of 50 users, 4 elaboration areas and 113 equipments were included. 435 components were parameterized (195 raw materials and 240 pharmaceutical specialties), 54 packaging materials, 376 standardised work procedures (123 of them corresponding to sterile medicines and 253 to non-sterile medicines, of which 52 non-sterile were dangerous), in addition, 17 were high risk, 327 medium risk, and 32 low risk, and 13 quality controls. CONCLUSIONS: The computerization of the production process has allowed the implementation of a traceability and secure manufacturing system in a controlled environment in accordance with current legislation.

Losartan potassium liquid formulation for paediatric hospital use: development and stability evaluation.

OBJECTIVES: This study aimed to develop a liquid oral formulation containing losartan potassium, an angiotensin II receptor antagonist drug used for its antihypertensive activity, and to perform a preliminary stability assessment under different temperatures and packages to ensure paediatric therapeutic adherence and facilitate the hospital routine. METHODS: A syrup containing losartan potassium (1.0 and 2.5 mg/mL) (excipients: potassium sorbate, sucrose (85%), water, citric acid and raspberry flavouring) was prepared. The packaging was carried out in amber polyethylene terephthalate (PET) and amber glass bottles (in triplicate) under the following conditions: (a) room temperature (15-30°C); (b) refrigeration (2-8°C); and (c) oven temperature (40°C) for 28 days. An analytical method by high performance liquid chromatography using a reverse-phase column was also developed and validated for quantitative determination of the drug in the formulations. RESULTS: The analytical method showed satisfactory linearity, detection and quantification limits, precision, accuracy and robustness. Samples at room temperature maintained content values between 90% and 110% for 7 days, while those stored under refrigeration maintained a homogeneous appearance and content between 90% and 110% for a period of 21 days. Values of pH stayed in a narrow range. Viscosity results were between 40.1 and 49.2 centipoise (cp) for glass bottles and 42.4 and 54.7 cp for PET bottles. CONCLUSIONS: A simple and economical losartan potassium liquid formulation was produced and was shown to be stable under refrigeration for 21 days in both PET and glass packages.

Contribution of hospital pharmacists to sustainable healthcare: a systematic review.

BACKGROUND: With a global annual carbon footprint of the healthcare sector of 2 gigatons of CO2e, healthcare systems must contribute to the fight against climate change. Hospital pharmacists could be key players in ecological transition due to their role in managing healthcare products. The aim of this study was to summarise the evidence on interventions implemented in healthcare facilities involving pharmacists to improve the environmental footprint of healthcare. METHODS: This systematic review was conducted following PRISMA 2020 guidelines. The Medline, Web of Science and ScienceDirect databases were searched for studies published between 2013 and 2023. To be eligible for inclusion, studies had to include hospital pharmacists and present contributions aimed at reducing the environmental footprint of healthcare in healthcare facilities. Outcomes were the description of the contribution, the methods used and the stages of healthcare product lifecycle analysed. A Mixed Methods Appraisal Tool was used to assess the risk of bias for each study. RESULTS: Seventeen studies were included. Pharmacists played a leading role in 15 (88%) and had a supporting role in the others. The healthcare products targeted were medicines (59%), medical devices (12%) or both (29%). The stages of the healthcare product cycle addressed by the contributions were elimination (71%), dispensing (35%), procurement and supply (35%), production (29%), and prescription (24%). Only two studies used life cycle assessment and only one assessed all three pillars of sustainability. Two studies had good methodological quality while the rest had at least one element of uncertainty. CONCLUSION: This review confirms the central role of the pharmacist and the importance of a multidisciplinary approach in implementing eco-responsible actions. It could be useful to hospitals and other teams wanting to improve sustainable actions and it emphasises the importance of collaborating with pharmacists when planning sustainable initiatives. Future eco-responsible initiatives must use robust reproducible methods. TRIAL REGISTRATION: PROSPERO #CRD42023406835.

Comparing visual inspection methods for parenteral products in hospital pharmacy: between reliability, cost, and operator formation considerations.

INTRODUCTION: The COVID-19 pandemic has led to unforeseen and novel manifestations, as illustrated by the management of drug shortages through the development of hospital production of sterile pharmaceutical preparations (P2S). Visual inspection of P2S is a release control whose methods are described in monographs of the European Pharmacopoeia (2.9.20) and the United States Pharmacopeia (1790). However, these non-automated visual methods require training and proficiency testing of personnel. The main objective of this work was to compare the reliability and speed of analysis of two visual methods and an automated method for detecting visible particles by image analysis in P2S. Furthermore, these methods were used to evaluate sources of particulate contamination during pre-production processes (washing, disinfection, depyrogenation) and production (filling, capping). MATERIALS AND METHODS: Three pharmacy technicians examined 41 clear glass vials of type I, 10 and/or 50 mL through manual visual inspection (MVI), semi-automated (SAVI), and automated (AVI) inspection. The vials were distributed as follows: (i) 16 vials of water for injection containing either glass particles (224 µm or 600 µm), stopper fragments, or textile fibres; (ii) five sterile injectable specialties; (iii) 20 vials of water for injection prepared under different pre-production conditions. RESULTS AND DISCUSSION: MVI and SAVI detected 100% of visible particles compared with 28% for AVI, which showed a deficiency in detecting textile fibres. All three methods correctly analysed P2S that did not contain visible particles. The three methods detected particles in vials maintained under International Organization for Standardization (ISO) 9 pre-production conditions. However, detections by (i) MVI and SAVI, and by (ii) AVI of particles contained in vials maintained under ISO 8 pre-production conditions were deemed satisfactory and unsatisfactory, respectively. CONCLUSION: The importance of visual inspection of P2S requires rapid, sensitive, and reliable detection methods. In this context, MVI and SAVI have proven to be more effective than AVI for a more competitive financial, training, and implementation investment.

Stability of clozapine tablets repackaged in dose administration aids using repackaging machines.

BACKGROUND: The use of dose administration aids in automated ward dispensing devices requires the repackaging of medications, which may impact their stability compared with the original manufacturer's packaging. OBJECTIVES: This study aimed to assess the physical and chemical stability of clozapine tablets for up to 84 days after repackaging. METHODS: A total of 900 tablets of clozapine 100 mg (Viatris) were repackaged and stored under five different conditions to conduct physical and chemical stability tests on days 0, 28, 56 and 84. The results were compared with control tablets in their original packaging. Visual inspections of tablet appearance were performed. Physical tests included assessments of mass uniformity, friability and resistance to crushing, following the standards of the European Pharmacopoeia 11th edition. The chemical stability was determined using ultra-high performance liquid chromatography with tandem-mass spectrometry detection (UHPLC-MS/MS) to measure clozapine concentration, N-desmethyl-clozapine, and monitor clozapine degradation to detect formation of any degradation products other than N-desmethyl-clozapine. RESULTS: Visual examination showed changes in the appearance of tablets only in those stored under UV light. Mass uniformity met standards for all tablets over 84 days. None passed the friability test due to tablet cracking after tumbling. A gradual deterioration in tablet hardness was observed with the resistance to crushing test. In terms of chemical stability, N-desmethyl-clozapine was undetected in any of the tablets stored under all conditions, and the mean concentration of clozapine remained within the target range over 84 days. CONCLUSION: N-desmethyl-clozapine was not detected and clozapine concentrations remained stable under all storage conditions. The tablets were compliant with the mass uniformity test in each condition. However, the tablets were cracked in the friability test and gradual deterioration in tablet hardness was observed. In the light of these results, the Vinatier Hospital pharmacy has chosen to establish a shelf life for clozapine tablets of 84 days.

Investigation of the hospital pharmacy profession in Europe.

OBJECTIVE: From 1995, the European Association of Hospital Pharmacists (EAHP) has regularly investigated the progress of the hospital pharmacy profession in Europe, and identified key barriers and drivers of this. The most recent 'Investigation of the Hospital Pharmacy Profession in Europe' was conducted from November 2022 to March 2023. METHODS: The online questionnaire was sent to all hospital pharmacies in EAHP member countries. The investigation was drafted using the same questions as the 2015 baseline survey. Where possible and relevant, responses were compared with the data from previous surveys that monitored the implementation of the EAHP statements. Keele University, Centre for Medicines Optimisation, School of Pharmacy and Bioengineering, UK analysed the data. RESULTS: The overall number of responses was 653, with a better response rate of 19% compared with 14% in 2018 statements survey. The findings indicated that participating hospital pharmacies have similar characteristics to previous surveys. Section 1 (Introductory statements and governance), section 2 (Selection, procurement and distribution), section 3 (Production and compounding), section 5 (Patient safety and quality assurance) questions were generally answered positively, with results ranging from 52% to 90%. However, results for section 4 (Clinical pharmacy services) returned lower levels of positivity, with responses from 8 of the 15 questions being less than 60%. When asked what is preventing hospital pharmacists from achieving implementation of these activities, most answers were limited capacity, not considered to be a priority by managers, or other healthcare professionals do this. The last section focused on self-assessment and action planning, with fewer than 50% of positive responses; COVID-19 preparedness and vaccines with mixed positive and negative responses. Furthermore, implementation of the falsified medicines directive impacted the medication handling processes in 50% or more of the answers. Regarding sustainability, the majority (59%) of respondents felt a greater focus should be on sustainability from an organisational or management perspective. CONCLUSION: Results offer valuable insights into the hospital pharmacy profession throughout Europe. While there have been improvements in certain areas, challenges remain, particularly in implementing clinical pharmacy services. The findings provide a foundation for further dialogue, advocacy, and strategic planning to advance the role of hospital pharmacists and enhance patient care in Europe's healthcare systems.

Implementation of a traceability system and safe manufacturing medications in a clean room. / Implantación de un sistema de trazabilidad y elaboración segura de medicamentos en la sala blanca.

OBJECTIVE: To describe the process of implementing a traceability and safe drug manufacturing system in the clean room of a Pharmacy Service to increase patient safety, in accordance with current legislation. METHODS: The process was carried out between September 2021 and July 2022. The software program integrated all the recommended stages of the manufacturing process outlined in the "Good Practices Guide for Medication Preparation in Pharmacy Services" (GBPP). The following sections were parameterized in the software program: personnel, facilities, equipment, starting materials, packaging materials, standardized work procedures, and quality controls. RESULTS: A total of 50 users, 4 elaboration areas and 113 equipments were included. 435 components were parameterized (195 raw materials and 240 pharmaceutical specialties), 54 packaging materials, 376 standardized work procedures (123 of them corresponding to sterile medicines and 253 to non-sterile medicines, of which 52 non-sterile were dangerous), in addition 17 were high risk, 327 medium risk, 32 low risk, and 13 quality controls. CONCLUSIONS: The computerization of the production process has allowed the implementation of a traceability and secure drug manufacturing system in a controlled environment in accordance with current legislation.

Detection and reduction of errors in parenteral nutrition compounding through gravimetric and product control. / [Artículo traducido] Detección y reducción de errores en la elaboración de la nutrición parenteral mediante control gravimétrico y de producto.

OBJECTIVE: To analyze the errors in the preparation of parenteral nutrition in a Pharmacy Service, detected through an already consolidated gravimetric and product quality control, and compare them with those detected during the initial years of implementing this quality control. METHODS: All errors detected through quality control in the compounding of pediatric and adult parenteral nutrition between 2019 and 2021 were prospectively analyzed. This quality control consisted of 3 sequential processes: a visual check, a gravimetric control, and a product control. Errors were classified as gravimetric, when the nutrition had a deviation of more than 5% from the theoretical weight, or as product errors when a qualitative or quantitative error was detected upon reviewing the remainder of the components used. These errors were analyzed in terms of type and the component involved. A comparison was made with the errors detected during the implementation phase of this quality control from 2016 to 2018. RESULTS: A total of 41,809 parenteral nutritions were reviewed, and 345 errors were detected (0.83% of the preparations); of these, 59 errors were found in pediatric nutritions (0.68% of them), and 286 in adult nutritions (0.86% of them). Among these errors, 193 were of gravimetric nature, while 152 were detected through product control. The main components involved in product errors were electrolytes, primarily due to the addition of excessive volumes and the use of incorrect components. A significant absolute reduction of 0.71% (p < 0.05) in the total number of errors was observed when compared to the implementation phase. This reduction was consistent in both gravimetric errors (-0.59%) and product-related errors (-0.12%) (p < 0.05). CONCLUSIONS: Comprehensive quality control of parenteral nutrition preparation is an easily implementable tool that effectively detected and prevented significant errors. Furthermore, its widespread adoption contributed to a reduction in the overall error count.

Physicochemical and biological stability of diluted vedolizumab in intravenous infusion bags.

INTRODUCTION: Intravenous vedolizumab is a widely used monoclonal antibody for outpatients with inflammatory bowel disease. Drug preparation is performed on the day of administration, but is time consuming, causing unnecessary in-hospital patient delay and inefficient logistics for preparation and distribution. Storage of vedolizumab ready-to-administer infusions and distribution via pneumatic air tubes could streamline logistics in the outpatient setting. The aim of this study was to test the shelf life and stability of ready-to-administer intravenous infusion bags containing vedolizumab. METHODS: For assessing in-use shelf life, the reconstituted product (300 mg fixed dose) was diluted to a concentration of 1.2 mg/mL in 0.9% NaCl under aseptic conditions, and stored in polyolefin infusion bags at 2-8°C prior to analysis. On replicate samples, we measured concentration, physical and chemical stability using sodium dodecyl sulphate polyacrylamide gel electrophoresis, size exclusion chromatography, and multi-angle laser light scattering, as well as biological activity using a biolayer interferometry assay to study target engagement, and endotoxin content to assess microbiological stability. Stability of ready-to-use vedolizumab was assessed also after transportation via pneumatic tube system. Samples were taken at different time points over an observation period of 30 days on four replicate samples. RESULTS: For all parameters assessed, the ready-to-use solution of vedolizumab remained stable over a period of at least 30 days. There were no signs of protein aggregation, chemical instability, or loss of binding of the antibody to the α4ß7 integrin target. There was no increase in endotoxin concentration over time. No significant difference was seen in antibody structural stability and protein aggregation between samples before and after transportation via pneumatic tube system. CONCLUSION: When prepared under aseptic conditions, dissolved ready-to-administer vedolizumab infusion bags can be stored long term at 2-8°C and transported via pneumatic air tube, without observable loss of antibody stability or binding activity.

Detection and reduction of errors in parenteral nutrition compounding through gravimetric and product control.

OBJECTIVE: To analyze the errors in the preparation of parenteral nutrition in a Pharmacy Service, detected through an already consolidated gravimetric and product quality control, and compare them with those detected during the initial years of implementing this quality control. METHODS: All errors detected through quality control in the compounding of pediatric and adult parenteral nutritions between 2019 and 2021 were prospectively analyzed. This quality control consisted of 3 sequential processes: a visual check, a gravimetric control, and a product control. Errors were classified as gravimetric, when the nutrition had a deviation of more than 5% from the theoretical weight, or as product errors when a qualitative or quantitative error was detected upon reviewing the remainder of the components used. These errors were analyzed in terms of type and the component involved. A comparison was made with the errors detected during the implementation phase of this quality control from 2016 to 2018. RESULTS: A total of 41,809 parenteral nutritions were reviewed, and 345 errors were detected (0.83% of the preparations); of these, 59 errors were found in pediatric nutritions (0.68% of them), and 286 in adult nutritions (0.86% of them). Among these errors, 193 were of gravimetric nature, while 152 were detected through product control. The main components involved in product errors were electrolytes, primarily due to the addition of excessive volumes and the use of incorrect components. A significant absolute reduction of 0.71% (P < .05) in the total number of errors was observed when compared to the implementation phase. This reduction was consistent in both gravimetric errors (-0.59%) and product-related errors (-0.12%) (P < .05). CONCLUSIONS: Comprehensive quality control of parenteral nutrition preparation is an easily implementable tool that effectively detected and prevented significant errors. Furthermore, its widespread adoption contributed to a reduction in the overall error count.

Medication use in a cohort of adults with chronic intestinal failure: A prospective cross-sectional study.

BACKGROUND: Oral drug therapy may be compromised in chronic intestinal failure (IF) because of alterations in absorption and transit. Only scarce literature is available on which medication patients with chronic IF take in daily life. The aim was to describe the medication use in these patients. METHODS: A medication history was obtained from adults with chronic IF treated in our tertiary care IF center. Degree of polypharmacy, drug classes, Biopharmaceutics Classification System classes, route of administration, and formulation of drugs were analyzed. RESULTS: From October 2019 until December 2020, 72 patients (35 patients with short bowel syndrome [SBS] and 37 patients without SBS) were included. Polypharmacy was seen in 85.7% of patients with SBS and 75.7% of patients without SBS. The top three drug classes were proton-pump inhibitors, vitamin D or acetaminophen, and antimotility medication or laxatives/benzodiazepines. Approximately 25% of the drugs were classified as Biopharmaceutics Classification System class I drugs. In patients with SBS (78%) and patients without SBS (74.9%), most medication was taken orally, requiring gastrointestinal absorption of the active substance to be pharmacologically active. Most of these medications (77% in patients with SBS and 80.8% in patients without SBS) were formulated as a capsule or tablet, requiring disintegration and dissolution in the gastrointestinal tract before absorption can take place. CONCLUSION: Polypharmacy was observed in most patients with chronic IF. Most medication was taken orally in formulations requiring disintegration, dissolution, and gastrointestinal absorption, which could be compromised in chronic IF.

Quality assurance standards and their use in the preparation of parenteral systemic anticancer therapy products in healthcare establishments: a scoping review.

OBJECTIVES: The use of parenteral systemic anticancer therapy (SACT) has led to improved cancer survival. A quality assurance (QA) system of the aseptic compounding process is necessary to ensure safe and consistent production of parenteral SACT. This scoping review identifies international evidence and practice relating to QA standards in the preparation of parenteral SACT in healthcare establishments. METHODS: Standards relating to aseptic compounding in hospital pharmacies and literature exploring the aseptic compounding of parenteral SACT were included. Literature relating to the non-aseptic compounding of medicines and records specific to sterile manufacturing in industrial settings were excluded. A search of several electronic databases, trial registries, the grey literature and websites of key European hospital pharmacy groups and accreditation bodies was conducted on 16 March 2022. A narrative discussion was performed by country, and content analysis of articles was conducted. RESULTS: Thirty-seven records were included. Standards reviewed covered the work environment, the preparation process and the safety of the workers who are potentially exposed to hazardous chemicals. It was a common practice to include frequent audits to ensure adherence to standards. Some standards also recommended external inspections to allow for further learnings. Periodic reviews are encouraged to ensure standards maintain relevance. National standards of the countries reviewed were based on international standards, with minor adaptations for local conditions. CONCLUSIONS: The main limitation of this review is that it is limited to countries with a high human development index. The review shows that the use of an internationally recognised standard as a basis for national standards is best practice, and will allow for relevance into the future.

Stability Study of a Compounded Sublingual Buprenorphine Solution for Neonatal Opioid Withdrawal Syndrome.

OBJECTIVE: Sublingual (SL) buprenorphine is a cornerstone of care in the treatment of adult opioid use disorder. Recent studies have demonstrated its advantages in the management of neonatal opioid withdrawal syndrome (NOWS). Commercially available SL tablets and transdermal patches are not amenable to neonatal use, and published compounding formulas of SL solutions contained undesirable excipients, including ethanol, sugars, and preservatives. The objective of this research is to explore the stability of a novel SL buprenorphine formulation free of alcohol, sugars, and preservatives. METHODS: A 0.075 mg/mL buprenorphine solution was prepared by diluting the commercial injectable solution with normal saline and packaged into polyethylene terephthalate amber prescription bottles and polypropylene amber oral syringes and stored in refrigeration. Quality assessments were conducted by visual, pH, and high-performance liquid chromatography (HPLC) analysis immediately after preparation, and at 7 and 14 days of storage. RESULTS: There were neither visual nor pH changes detected through 14 days. HPLC analysis indicated that all samples retained >99% initial buprenorphine concentration. Drug concentration increased slightly in the oral syringe after day 7, probably due to moisture loss. No degradation peaks were observed in chromatograms. CONCLUSIONS: This novel buprenorphine is free of alcohol, sugar, and preservatives, and it may offer a significant safety advantage for NOWS patients. Additional clinical studies are recommended to verify the bioavailability and efficacy of this formulation.

Capillary electrophoresis in parenteral nutrition control - validation of two analytical methods: Amino acids/glucose/glucose-1-phosphate and K/Na/Ca/Mg.

OBJECTIVES: Production of parenteral nutrition bags (PNBs) involves many nutrients: complete control of the production process decreases the risk of error. This study aimed to develop and validate two analytical methods by capillary electrophoresis (CE) for simultaneous detection of: glucose, amino acids (Primene®) and glucose-1-phosphate (Phocytan®) (anionic method, AM) on one hand; and on the other hand potassium, sodium, calcium and magnesium (cationic method, CM). METHODS: Methods were developed using capillary electrophoresis with diode array detection (CE-DAD) (CE 7100, Agilent), indirect photometric detection, 56 cm long capillary and two different buffers (pH=12.1 for AM and pH=3.2 for CM). These methods were validated according to guidelines from the Société Française des Sciences et Techniques Pharmaceutiques (SFSTP).Analytical parameters were optimised: temperature was regulated at 15°C and the current settled to - 15kV, for a 21 minute analysis time for AM. Conditions were settled to 25°C and 30kV for CM so the analysis time dropped to 7 minutes.Accuracy profiles were established and recovery rates (RR), Repeatability and Reproducibility Coefficient of Variation (respectively RaCV and RoCV) were calculated.Capability was also calculated for each nutrient and concentration range according to guidelines from the Evaluation and Research Group on Protection in a Controlled Atmosphere (GERPAC). RESULTS: Methods were successfully validated with: RR between 99.2 and 101.9%, RaCV between 1.5 and 3.1%, and RoCV between 2.4 and 4.1% for AM, and RR between 97.5 and 102.7%, RaCV between 0.5 and 2.3%, and RoCV between 0.6 and 2.8% for CM.Accuracy profiles were established with 95% ß probability, except for glucose-1-phosphate (90%). Acceptance limits were settled to ±1 0% of target value. Capabilities are defined as "good" or "very good". CONCLUSIONS: The methods developed by this research will ensure the composition of PNB is compliant to PNB formulas. These results show CE is an appropriate method for PNB quantitative control.CE utilisation for controlling other hospital preparations seems to be a relevant alternative to conventional methods such as liquid chromatography.