BACKGROUND: Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs). METHODS: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure. RESULTS: In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003). CONCLUSION This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.
Antirheumatic Agents/adverse effects* ; Arthritis, Rheumatoid/drug therapy* ; Humans ; Network Meta-Analysis ; Pharmaceutical Preparations ; Randomized Controlled Trials as Topic ; Tuberculosis/drug therapy*

This study aims to explore the evaluation model for the proficiency testing of heavy metal and harmful element residues in pharmaceuticals,and to provide reference for the proficiency testing program and proficiency testing result in the field of residue analysis. The proficiency test result of cadmium determination in honeysuckle as an example. The algorithm A,NIQR,and Horwitz function are used to calculate the assigned value and the standard deviation. Z was obtained at the same time. If | Z | ≤2,the result is satisfactory. If 2< | Z | <3,the result is questionable. If | Z | ≥3,the result is unsatisfactory. In addition,the median value is the assigned value,and deviation(D%) is used. If D% is not more than 16%,the result is satisfactory; if D% is more than 16%,the result is unsatisfactory. After analysis,in the results of questionable or dissatisfied laboratories calculated by algorithm A and NIQR,the deviation error of some data is within the scope of the standard. In the results of the satisfactory laboratory evaluated by the Horwitz function,some data deviation errors far exceed the standard range. The evaluation result of the D% meets the requirements. According to heavy metal and harmful element trace analysis methods,this study is the first to apply D% to the evaluation of the detection ability of heavy metals and harmful elements in pharmaceuticals. This method makes the evaluation result more reasonable,and has important reference significance for the evaluation of other proficiency test results.
Cadmium ; analysis ; Laboratories ; Laboratory Proficiency Testing ; Lonicera ; chemistry ; Pharmaceutical Preparations ; standards ; Plant Preparations ; standards ; Trace Elements ; analysis

The content of ATP, ADP, AMP, sodium phosphate and sodium pyrophosphate were determined by 31P NMR, the linear range of ATP, ADP and AMP were found to be 0.004-0.080 mol x L(-1), sodium phosphate and sodium pyrophosphate were 0.005-0.100 mol x L(-1). The RSD were 0.40%-1.30%, the recovery were 96.9% - 105.2%. The method has been applied to the determination of ATP injection. The impurities of ATP injection were ADP and sodium phosphate. The content of ATP is in line with the requirement of the pharmacopoeia. The results indicated that the method is of good reproducibility, high accuracy, rapid and simple operation, without pretreatment and interference of other elements, 31P NMR is a new and reliable method of analyzing ATP, ADP, AMP and phosphate.
Adenosine Diphosphate ; analysis ; Adenosine Monophosphate ; analysis ; Adenosine Triphosphate ; analysis ; Chemistry, Pharmaceutical ; methods ; Diphosphates ; analysis ; Magnetic Resonance Spectroscopy ; Perfusion ; Pharmaceutical Preparations ; analysis ; Phosphates ; analysis ; Quality Control ; Reproducibility of Results

Pharmacoeconomics is an important part of the postmarketing Chinese medicine (CM) evaluation, and postmarketing pharmacoeconomic evaluation can reveal the clinical and market value of CM. The purpose of establishing the guideline for pharmacoeconomic evaluation is to make the evaluation process and results regarding Chinese patent medicines both scientific and fair. Every country's guidelines for pharmacoeconomic evaluation act as reference guidelines, we have already drawn up the guideline that takes into account the special characteristics of CM; and these are in preparation for the postmarketing CM pharmacoeconomic evaluation.
Clinical Trials as Topic ; Cost-Benefit Analysis ; Economics, Pharmaceutical ; Guidelines as Topic ; Humans ; Pharmaceutical Preparations ; economics ; Product Surveillance, Postmarketing ; economics ; Statistics as Topic

In order to reaction the quality present situation, problems on the current quality of animal sources of drugs are summed up by using test data analysis, literature search and marketing research. This paper can also help the improvement of the quality management, the revision of the relevant department policy system and the improvement of standards.
Animals ; China ; Medicine, Chinese Traditional ; standards ; Pharmaceutical Preparations ; analysis ; standards ; Quality Control

The marine biological source of mineral drugs recorded in Chinese Pharmacopoeia (2010 version) mainly including pearl, nacre, clam shell, common oyster shell, ark shell, cuttle bone, and sea-ear shell are widely used in clinical. Calcium carbonate and a small amount of protein are the main components in this type of drugs. In this paper, a systematical and comparable study were carried out by determination of calcium carbonate by EDTA titration method, the crystal of calcium carbonate by X-Ray powder diffraction and the total amino acids (TAAs) of the hydrolyzed samples by ultraviolet spectrophotometry method. As a result, the crystal structure is calcite for common oyster shell, mixture of calcite and aragonite for nacre and sea-ear shell, aragonite for the other drugs. The content of calcium carbonate ranged from 86% to 96%. Cuttle bone has the highest amount of TAAs among the seven drugs which reached 1.7% while clam shell has the lowest content of 0.16% on average. In conclusion, an effective method was developed for the quality control of marine mineral drugs by comprehensive analysis of calcium carbonate and TAAs in the seven marine mineral drugs.
Amino Acids ; analysis ; chemistry ; Animal Shells ; chemistry ; Animals ; Calcium Carbonate ; analysis ; chemistry ; Crystallization ; Edetic Acid ; chemistry ; Mollusca ; chemistry ; classification ; Pharmaceutical Preparations ; analysis ; chemistry ; standards ; Quality Control ; Reproducibility of Results ; Seawater ; Species Specificity ; Spectrophotometry, Ultraviolet ; X-Ray Diffraction

The release behavior of single pellet was investigated by LC/MS/MS method with tamsulosin hydrochloride (TSH) as the model drug of the research and then the pellets were divided into four groups according to the drug loading. Comparison of dissolution profiles of each group and capsule were performed using f1 and f2 factor methods to study the difference and similarity. The release profiles of single pellet, each group and capsule were analyzed using principle component analysis (PCA). The particle system was built through Matlab to get the target release profile. The result of this research demonstrated the release behavior of single pellet correlated well with the drug loading. While the dissolution profile of capsule as a reference, the similarity factor of dissolution profiles of the lower drug loading groups were 62.2, 67.1, 53.9, respectively and, 43.3 for highest drug loading group. The particle systems with different pellet distribution and same release profiles were built through release behavior of single pellet. It is of significance to investigate the release behavior of single pellets for studying the release regularity of multiple-unit drug delivery system.
Capsules ; Chemistry, Pharmaceutical ; Chromatography, Liquid ; Delayed-Action Preparations ; Drug Delivery Systems ; Drug Liberation ; Principal Component Analysis ; Sulfonamides ; administration & dosage ; chemistry ; Tandem Mass Spectrometry ; Technology, Pharmaceutical

This paper reports the determination of the drug antibody ratio in an antibody-drug conjugate with two methods, i.e. LC-MS and UV/VIS, and to provide a reliable method to scientifically evaluate and effectively control the drug antibody ratio. Deglycosylated sample was analyzed with C4 column followed by MS, and the number of conjugated drugs in the antibody was determined by the molecular weight increase due to the addition of different number of drugs to the antibody, and then drug antibody ratio was calculated by weighted average of different number of drugs conjugated to the antibody. Optical density at 252 and 280 nm was measured with UV/VIS, and due to the difference of extinction coefficients between the antibody and the drug, the drug antibody ratio was calculated from linear equation with two unknowns. The drug antibody ratio was 3.21 and 3.25 respectively measured by the two methods, and the results were similar with the two methods. Our study indicated that both methods, LC-MS and UV/VIS, could be applied to the analysis of drug antibody ratio of the antibody drug conjugate.
Antibodies ; analysis ; chemistry ; Gas Chromatography-Mass Spectrometry ; methods ; Glycosylation ; Immunoconjugates ; analysis ; chemistry ; Maleimides ; analysis ; chemistry ; Molecular Weight ; Pharmaceutical Preparations ; analysis ; chemistry ; Spectrophotometry, Ultraviolet ; methods

The present work is to investigate the correlation between physical properties and deformation behaviors of tablet excipients, and rank them according to their plastic performances during compaction. The excipients selected were compacted using Korsch XP1 after measuring their physical properties where the compression parameters for evaluating deformation behaviors were Heckle equation, compression work and elastic stretch in die. The correlations between compaction descriptors and physical parameters were analyzed by canonical correlation analysis, and factor analysis was simultaneously employed to synthetically assess deformation behaviors for all our samples. The canonical variables show that true density (Pa) correlated negatively with plastic coefficient (PL) and positively with yield pressure (YP); compression degree (Cp) correlated negatively with fast elastic stretch (FES) as well as YP and positively with PL. When factor scores were used in combination with original data, the plasticity of our samples was sorted and ranked as high (-0.56 < F' < 0.21), intermediate (-0.16 < F' < 0.36), or low (0.38 < F' < 0.84), which are in accord with plasticity rankings previously reported in literature. This study indicates factor analysis can be an approach to evaluate deformation behaviors of pharmaceutical powders.
Chemistry, Pharmaceutical ; methods ; Compressive Strength ; Elasticity ; Excipients ; chemistry ; Factor Analysis, Statistical ; Particle Size ; Pharmaceutical Preparations ; chemistry ; Powders ; chemistry ; Pressure ; Tablets

This proficiency testing program is established to evaluate the pharmaceutical preparation analysis capacity of laboratories recommended by 18 countries and economies. It was authorized by Asia Pacific Laboratory Accreditation Cooperation (APLAC), and organized by Shanghai Institute for Food and Drug Control (SIFDC) and China National Accreditation Service for Conformity Assessment (CNAS). The 0.3sigma test is used to evaluate the homogeneity and stability of the proficiency testing sample. The results of the laboratories were assessed by Z-score. The robust average and the robust standard deviation of the participants' results were calculated as assigned value and standard deviation for performance assessment of hydrochlorothiazide and captopril using robust statistics. Thirty-three of 38 laboratories recommended by 18 countries and economies sent their results back. Twenty-four laboratories' results were observed as satisfactory. Five laboratories were identified as having reported at least one questionable result. Four laboratories were identified as having reported at least one unsatisfactory result.
Accreditation ; Captopril ; analysis ; Drug Combinations ; Drug Stability ; Hydrochlorothiazide ; analysis ; Laboratory Proficiency Testing ; Pharmaceutical Preparations ; chemistry