Weight change following knee and hip joint arthroplasty-a six-month prospective study of adults with osteoarthritis.

BACKGROUND: Inconsistent findings of weight change following total knee (TKA) and hip (THA) arthroplasty may largely be attributable to heterogeneous cohorts and varied definitions of weight loss. This study examined weight change following TKA and THA for osteoarthritis (OA). METHODS: 64 participants with hip or knee OA were recruited from orthopaedic joint arthroplasty waiting lists at a single major Australian public hospital between March and October 2011. The Short Form (SF) 12 survey was used to assess baseline physical and mental functioning. 49 participants completed 6 month follow-up (20 from the THA group and 29 from the TKA group). RESULTS: The majority of subjects lost weight (>0 kg) 6 months following THA (70 %) and TKA (58.6 %). When at least a 5 % reduction in total body weight was used to define clinically significant weight loss, the proportion of people with weight loss was 37.9 % for TKA and 25 % for THA. Greater weight loss occurred 6 months following TKA compared with THA (7.2 % versus 3.7 % of body weight; p = 0.04). Worse pre-operative physical functioning (SF-12) was associated with greater weight loss following TKA (ß = 0.22 kg, 95 % CI 0.02-0.42 kg; p = 0.04). CONCLUSION: Most people lost weight (>0 kg) 6 months following TKA and THA and a considerable proportion of people achieved ≥5 % loss of body weight. The magnitude of weight loss was greater following TKA than THA, with worse pre-operative function being a predictor of more weight loss. Further attention to weight management is required to assist a greater number of people to achieve a larger magnitude of weight loss following knee and hip joint arthroplasty.

A chemometric model for the quantitative determination of isotopic impurities in d3-methylamine hydrochloride by Fourier-transform infrared spectroscopy.

Deuterated drug molecules are of increasing interest to the pharmaceutical industry due to their capacity to slow metabolism and the potential for improved pharmacokinetics or improved pharmacodynamics they may offer over their non-deuterated counterparts. The desired level of deuteration or isotopic purity is a critical quality attribute for these compounds that can be essential for drug efficacy or patient safety. Deuterated reagents are often used to introduce a deuterated moiety into the drug substance; as such, isotopic impurities in these deuterated input materials need to be tightly controlled. A novel Fourier-transform infrared (FTIR) spectroscopic method was developed and evaluated as a fast and straightforward technique to quantify low-level isotopic impurities in the deuterated reagent d3-methylamine hydrochloride. Using data acquired through LC-MS analysis, the resulting chemometric model was validated according to ICH Q2(R1) guidelines achieving limits of quantitation of 0.31, 0.31, and 0.34 wt% for d0-, d1- and d2-methylamine hydrochloride impurities respectively.

Determination of residual acetone and acetone related impurities in drug product intermediates prepared as Spray Dried Dispersions (SDD) using gas chromatography with headspace autosampling (GCHS).

Spray Dried Dispersions (SDD) are uniform mixtures of a specific ratio of amorphous active pharmaceutical ingredient (API) and polymer prepared via a spray drying process. Volatile solvents are employed during spray drying to facilitate the formation of the SDD material. Following manufacture, analytical methodology is required to determine residual levels of the spray drying solvent and its associated impurities. Due to the high level of polymer in the SDD samples, direct liquid injection with Gas Chromatography (GC) is not a viable option for analysis. This work describes the development and validation of an analytical approach to determine residual levels of acetone and acetone related impurities, mesityl oxide (MO) and diacetone alcohol (DAA), in drug product intermediates prepared as SDDs using GC with headspace (HS) autosampling. The method development for these analytes presented a number of analytical challenges which had to be overcome before the levels of the volatiles of interest could be accurately quantified. GCHS could be used after two critical factors were implemented; (1) calculation and application of conversion factors to 'correct' for the reactions occurring between acetone, MO and DAA during generation of the headspace volume for analysis, and the addition of an equivalent amount of polymer into all reference solutions used for quantitation to ensure comparability between the headspace volumes generated for both samples and external standards. This work describes the method development and optimisation of the standard preparation, the headspace autosampler operating parameters and the chromatographic conditions, together with a summary of the validation of the methodology. The approach has been demonstrated to be robust and suitable to accurately determine levels of acetone, MO and DAA in SDD materials over the linear concentration range 0.008-0.4µL/mL, with minimum quantitation limits of 20ppm for acetone and MO, and 80ppm for DAA.

Determination of 2-Hydroxypyridine-1-Oxide (HOPO) at sub-ppm levels using derivitization and gas chromatography with mass spectrometry detection (GCMS).

This work describes the development and validation of an analytical method to determine residual trace levels of 2-Hydroxypyridine-1-Oxide (HOPO) in an active pharmaceutical ingredient (API). A method was required to be specific and sensitive enough to determine sub-ppm levels of this reagent. The approach taken to use a derivitization step overcame two of the primary challenges associated with the analysis of HOPO. Firstly, HOPO can tautomerize and the derivitization step provides a single stable entity to monitor, and secondly, the reaction enhances the volatility of the analyte to facilitate the use of gas chromatography. Mass spectrometry detection provides both suitable specificity and sensitivity. This paper describes the method development and optimisation of the derivitization step, the chromatographic conditions and mass spectrometry detection, together with a summary of the validation of the method. The method has been demonstrated to be robust and suitable to determine HOPO levels in commercially manufactured API materials.