The efficacy and safety of hydrotherapy in patients with knee osteoarthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis (OA) is a common clinical degenerative disease of the joints, which is prone to occur in middle-aged and elderly people. At present, the disease cannot be cured, it is mostly treated with drugs to relieve symptoms, improve joint function, protect cartilage, such as glucosamine, anti-inflammatory and analgesic drugs, and but the efficacy is not lasting and the recurrence rate is high. Hydrotherapy has become a long-term alternative therapy in China and is receiving increasing attention. We perform a protocol for systematic review and meta-analysis to determine the efficacy and safety of a hydrotherapy program in individuals living with knee OA. METHODS: This protocol will be designed in accordance with the preferred reporting items for systematic reviews and meta-analysis protocols. It is registered on the international prospective register of systematic reviews (No. CRD42022365564). We will search the following databases: The Cochrane Skin Group Trials Register, MEDLINE, EMBASE, The Cochrane central register of controlled trials, Chinese biomedical literature database, Chinese medical current content and China national knowledge infrastructure. The risk of bias of the included studies will be appraised using the Cochrane collaboration tool. Statistical analysis will be performed using IBM SPSS Statistics (Armonk, NY). RESULTS: This systematic review will summarize the short- and long-term clinical outcomes of hydrotherapy for knee OA. CONCLUSION: The findings from this review will establish the quality of currently available evidence, which will determine the need for further studies to establish the true effect size of hydrotherapy in knee OA.

Simultaneous determination of eight short-chain aliphatic amines in drug substances by HPLC with diode array detection after derivatization with halonitrobenzenes.

Short-chain aliphatic amines are a class of hazardous impurities in drug substances. A simple method, involving derivatization followed by high-performance liquid chromatography with diode array detection, has been developed for residue determination of eight aliphatic amines simultaneously in drug substances. Different halonitrobenzenes derivatization reagents were systematically compared. As a result, 1-fluoro-2-nitro-4-(trifluoromethyl)benzene was selected since the derivatization effectively shifted the absorption wavelength to the visible region (400-450 nm), where most drug substances, impurities and even the derivatization reagent absorb very weakly. Due to the redshift effect, interference was minimized and adequately low limits of quantitation were reached (0.24-0.80 nmol/mL). Moreover, the derivatization reaction was readily carried out in dimethyl sulfoxide at room temperature for 1 h using N,N-diisopropylethylamine as catalyst to achieve the highest yield. Without any pre-treatment, the derivatives were analyzed by high-performance liquid chromatography with diode array detection. The high stability of the derivatives within 24 h at room temperature (RSD<1.04%) further facilitated the simultaneous preparation and consecutive analysis of quantities of samples. Finally, the proposed method was successfully applied for residue determination of eight aliphatic amines simultaneously in eight drug substance samples. This study could be helpful for the routine analysis and residue control of aliphatic amines in drug substances.

Determination of small halogenated carboxylic acid residues in drug substances by high performance liquid chromatography-diode array detection following derivatization with nitro-substituted phenylhydrazines.

A method for the determination of small halogenated carboxylic acid (HCA) residues in drug substances is urgently needed because of the potential of HCAs for genotoxicity and carcinogenicity in humans. We have now developed a simple method, involving derivatization followed by high performance liquid chromatography-diode array detection (HPLC-DAD), for the determination of six likely residual HCAs (monochloroacetic acid, monobromoacetic acid, dichloroacetic acid, 2-chloropropionic acid, 2-bromopropionic acid and 3-chloropropionic acid) in drug substances. Different nitro-substituted phenylhydrazines (NPHs) derivatization reagents were systematically compared and evaluated. 2-Nitrophenylhydrazine hydrochloride (2-NPH·HCl) was selected as the most suitable choice since its derivatives absorb strongly at 392 nm, a region of the spectrum where most drug substances and impurities absorb very weakly. During the derivatization process, the commonly used catalyst, pyridine, caused rapid dechlorination or chlorine substitution of α-halogenated derivatives. To avoid these unwanted side reactions, a reliable derivatization method that did not use pyridine was developed. Reaction with 2-NPH·HCl using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride as coupling agent in acetonitrile-water (70:30) at room temperature for 2h gave complete reaction and avoided degradation products. The derivatives were analyzed, without any pretreatment, using gradient HPLC with detection in the near visible region. Organic acids commonly found in drug substances and other impurities did not interfere with the analysis. Good linearity (r>0.999) and low limits of quantitation (0.05-0.12 µg mL(-1)) were obtained. The mean recoveries were in the range of 80-115% with RSD <5.81% except for 3-CPA in ibuprofen which was 78.5%. The intra- and inter-day precisions were expressed as RSD <1.98% and <4.39%, respectively. Finally, the proposed method was successfully used for the residue determination of the six HCAs in eight drug substance samples.